Next Article in Journal
Greater Efficacy of Black Ginseng (CJ EnerG) over Red Ginseng against Lethal Influenza A Virus Infection
Next Article in Special Issue
Effect of Bread Structure and In Vitro Oral Processing Methods in Bolus Disintegration and Glycemic Index
Previous Article in Journal
Dietary Patterns and Renal Health Outcomes in the General Population: A Review Focusing on Prospective Studies
Previous Article in Special Issue
Abscisic Acid Standardized Fig (Ficus carica) Extracts Ameliorate Postprandial Glycemic and Insulinemic Responses in Healthy Adults
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Nutrients
Volume 11
Issue 8
10.3390/nu11081878
nutrients-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Discussion

Incretin Hormones: The Link between Glycemic Index and Cardiometabolic Diseases

by
Teresa Salvatore
1,
Riccardo Nevola
2,
Pia Clara Pafundi
2,
Lucio Monaco
2,
Carmen Ricozzi
2,
Simona Imbriani
2,
Luca Rinaldi
2 and
Ferdinando Carlo Sasso
2,*
1
Unit of Internal Medicine, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia, 2, 80138 Naples, Italy
2
Unit of Internal Medicine, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Piazza Miraglia, 2, 80138 Naples, Italy
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(8), 1878; https://doi.org/10.3390/nu11081878
Submission received: 30 June 2019 / Revised: 7 August 2019 / Accepted: 8 August 2019 / Published: 13 August 2019
(This article belongs to the Special Issue The Relationship between Glycemic Index and Human Health)
Versions Notes

Abstract

:
This review aimed to describe the potential mechanisms by which incretin hormones could mediate the relationship between glycemic index and cardiometabolic diseases. A body of evidence from many studies suggests that low glycemic index (GI) diets reduces the risk for type 2 diabetes and coronary heart disease. In fact, despite the extensive literature on this topic, the mechanisms underlying unfavorable effects of high GI foods on health remain not well defined. The postprandial and hormonal milieu could play a key role in the relationship between GI and cardiovascular risk. Incretin hormones, glucagon-like peptide1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are important regulators of postprandial homeostasis by amplifying insulin secretory responses. Response of GIP and GLP-1 to GI have been studied more in depth, also by several studies on isomaltulose, which have been taken as an ideal model to investigate the kinetics of incretin secretion in response to foods’ GI. In addition, extrapancreatic effects of these incretin hormones were also recently observed. Emerging from this have been exciting effects on several targets, such as body weight regulation, lipid metabolism, white adipose tissue, cardiovascular system, kidney, and liver, which may importantly affect the health status.

1. Introduction

High carbohydrates diets, especially from refined sources such as white rice and white bread, starches, and added sugars, are associated with an increased risk of cardiovascular events and all-cause mortality [1].
It has become clear that not all carbohydrates are the same and that post meal rise in glucose levels is mainly influenced by carbohydrates’ quality and other food-related compounds rather than by carbohydrate quantity per se.
The glycemic index (GI) is a measure of blood glucose increase elicited by foods, computed from the incremental area under the postprandial plasma glucose curve of a test food, expressed as percentage of that of an equal amount (typically 50 g, at times 25 g) of a reference carbohydrate (e.g., glucose or white bread) [2]. Even if its relevance still continues to be an object of debate, GI represents a property of the food itself, precisely defined by the International Organization for Standardization (ISO) method 26,642:2010 and a methodology sufficiently valid and reproducible for discriminating foods based on their glucose response [2].
Quality of carbohydrates as defined by GI can markedly affect the health status. In particular, consumption of high-GI foods has been described to increase the risk for noncommunicable diseases such as obesity, type 2 diabetes, and cardiovascular diseases [2,3]. Several prospective cohort studies suggest that low GI diets reduce the risk for type 2 diabetes and coronary heart disease [4,5,6].
Despite the extensive literature on this issue, the mechanisms underlying unfavorable effects of high GI foods on health still remain not well defined. The main role has been historically attributed to postprandial hyperglycemia, along with related hyperinsulinemia [7]. However, the postprandial metabolic and hormonal milieu is a very complex pathophysiological state, as many factors outside of blood glucose and insulin levels may be implicated. In this context, insulin secretory responses initiated by post-meal hyperglycaemia are notably amplified by incretin hormones, a phenomenon called “incretin effect” and attributed to the release of incretin hormones from specialized entero-endocrine cells elicited by absorption of oral glucose but not by intravenous glucose administration. Thus, incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) may be important regulators of postprandial homeostasis [8].
The relationship between GI and healthy status is not clear, but several observations support a role for inflammatory as well as oxidative stress in foods with high GI. In particular, after a three-month reduction diet with low glycemic index, an increased level of IGF-I with cardioprotective effect was observed [9]. Moreover, a three-month intervention using a low glycemic index diet decreases inflammation by increasing the concentration of uric acid and the activity of glutathione peroxidase [10].
Since rates of glucose absorption closely related to GI of foods trigger a different pattern of incretin response, and a variety of pancreatic and extrapancreatic effects have been described for these gut-derived hormones, a role for GIP and GLP-1 in mediating GI effects on health status may be reasonably supposed. In this light, this review aimed to describe the potential mechanisms by which incretin hormones could mediate the relationship between glycemic index and cardiometabolic diseases.

2. Pancreatic Effects of Incretin Hormones

The majority of GIP producing K cells are found in the proximal small intestine and the duodenum, while GLP-1 producing L cells are much more dispersed, with a gradient from a low density in the duodenum to a higher density in the ileum, but also in the colon and rectum [11].
In fasting state, healthy human subjects have basal plasma concentrations for both incretins in the low picomolar range (10−12 mol L−1). These start to rise a few minutes after meal, reaching a peak after approximately 1 h, and returning to basal levels after several hours [11]. Nutrients stimulating incretin secretion are glucose and other carbohydrates (including sucrose and starch), triglycerides, and some aminoacids [12], whereas proteins are a comparatively weak stimulus.
Upon release, GIP and GLP-1 bind to specific G-protein coupled receptors present on ß-cells, where they exert additive effects on the stimulation of insulin secretion in a glucose-dependent manner [13]. Incretin hormones always require a permissive degree of hyperglycaemia to exert their insulinotropic action. Activation of protein kinase A elicited by the binding of incretins to their respective receptors cannot initiate the release of preformed insulin secretory granules from ß-cells, without closing of potassium channels, depolarization, and calcium ion influx, as determined by hyperglycemia. For the same reason, incretins cannot provoke episodes of hypoglycemia. For GLP-1, the absolute glycemic threshold below which insulin secretion cannot be stimulated, even at supra-physiological concentrations, has been identified as approximately 66 mg/dL [11]. This cut-off appears safe in particular in non-diabetic people, as these subjects generally show hypoglycemic symptoms for serum glycemic values below 50 mg/dL.
Incretin release is related to a meal by definition and depends on rates of nutrient entry into the small intestine to reach K and L cells [14]. Because of the more proximate location of GIP-producing K cells, the necessary gastric delivery, both in terms of food volume and glycemic content, is lower for GIP than GLP-1, even if studies in isolated perfused proximal small intestine suggest that both incretin responses to nutrients are elicited simultaneously [15].
Apart from insulin stimulation, GLP-1 reduces glucose concentrations by inhibiting α-cell glucagon secretion at all glucose levels and beyond the inhibition caused by blood glucose lowering alone [16]. GIP equally contributes with GLP-1 to the incretin effect, but unlike GLP-1 did not affect glucagon secretion.
In β-cells, GLP-1 not only enhances glucose-dependent insulin secretion and insulin synthesis, but, as described in animal studies, also stimulates β-cell proliferation and inhibits apoptosis, thus preserving β-cell function [17]. Whether this eventual regulation of β-cell mass in humans translates into a beneficial impact on diabetes progression still remains less elucidated.
Therefore, the pancreatic effects of GLP-1 and GIP are fundamentally similar, with the exception of the inhibitory effect on glucagon secretion performed only by GLP-1.

3. Relationship between Incretin Hormones and GI

3.1. Response of GIP and GLP-1 to Food Intake

Many studies have documented the response of incretin hormones to bread, reporting conflicting results. Fiber-enriched [18] and cereal-based [19] breads have been reported to reduce GIP secretion compared with white bread. A study [20] evaluating the five most common breads consumed in Spain, discovered that GIP release was higher after intake of wholemeal rather than white bread. Wheat bread consumption with different particle size elicited a GLP-1 response much lower after bread prepared with flour and 85% broken wheat kernels compared to a control bread made from wheat flour combined with wheat bran to obtain a similar fiber content [21].
Hartvigsen et al. [22] reported that only rye bread with kerornels may decrease GIP and GLP-1 postprandial secretion. Other authors have described no differential effect of white wheat or whole-grain breads on both incretins [23,24].
This wide variability of response probably depends on the fact that carbohydrates exert a different effect if ingested alone or into a food matrix such as bread. Many factors, among which manufacturing conditions, type of cereals, starch structure, bread particle size and inclusion of other ingredients, may affect the glycemic and incretin responses. In general, the glycemic response of a food is altered in the presence of other foods depending on the amount and source of carbohydrate and the amounts and types of fat and protein added. Moreover, other factors may influence entero-hormone release. Short chain fatty acids, produced during fermentation of unabsorbed carbohydrates or fiber by the intestinal microbiota, may stimulate GLP-1 secretion [25]. Bile acids are also able to potentiate GLP-1 release by activating their receptor TGR5 [26,27,28].

3.2. The Isomaltulose Model

Isomaltulose (6-O-D-glucopyranosyl-D-fructofuranose, Palatinose) is a disaccharide found in nature in honey and sugar cane, which has the same composition (one glucose molecule and one fructose molecule) and caloric value (4 kcal/g) as sucrose [29,30]. In industry, isomaltulose is manufactured using the enzyme glycosyltransferase, which converts the α-1,2 bond of sucrose into a α-1,6 bond [31].
Isomaltulose and sucrose are degraded respectively by isomaltase and sucrase, disaccharide-degrading enzymes located in small intestinal villi. In healthy subjects, isomaltulose is completely hydrolyzed at much lower rate than sucrose, thus determining slower rates of blood glucose and insulin increase as compared with sucrose [32,33]. The resulting monosaccharides (glucose and fructose) are completely absorbed by the small intestine [34,35] and do not reach the larger intestine, where alteration of microbioma might affect postprandial glucose responses [36]. Consequently, isomaltulose releases the same amount of energy as sucrose as confirmed in animal studies [32].
Based on these intrinsic characteristics, isomaltulose represents the ideal model to investigate the kinetics of incretin secretion in response to foods GI.
Studies on rats report that isomaltulose ingestion is characterized by reduced postprandial insulin and GIP release [37] and ileal administration of isomaltulose in anesthetized animals triggers a greater response of GIP than jejunal administration [38].
In the first human study [39] on the kinetics of incretin secretion elicited by isomaltulose, both plasma glucose and insulin levels resulted significantly lower, and total GIP secretion significantly and dramatically smaller, after isomaltulose than after sucrose loading. In contrast, GLP-1 levels observed at later time-points were significantly higher with isomaltulose than sucrose, as well as glucose and insulin levels at 120 min.
In a randomized, double-blind, crossover study on type 2 diabetic patients [40], postprandial glucose metabolism was characterized by using a combination of euglycemic-hyperinsulinemic clamp and labeled oral isomaltulose or sucrose load. Consistently with the previous report [39], absorption of isomaltulose was prolonged by on the 22-08-201950 min with respect to sucrose. Mean plasma concentrations of insulin, C-peptide, glucagon, and GIP were 10–23% lower. In contrast, GLP-1 was 64% higher after isomaltulose ingestion. Similarly, in another study [41] on type 2 diabetic participants, the incremental area under the curve of GIP was substantially reduced by 40% and that of GLP-1 remarkably and significantly 6.3-fold higher following isomaltulose than sucrose intake.
Keller et al. [42] reported that sugar sweetened beverages with isomaltulose (containing 50% fructose) led to significantly higher GLP-1 release compared to maltodextrin-sucrose intake (containing only 12.5% fructose), although GLP-1 response has been shown to be lower after pure fructose intake when compared with an equicaloric glucose load [43]. This result likely depends on the slower degradation of the α-1,6 glycosidic bond of isomaltulose and a higher proportion of glucose reaching the distal part of the ileum.
Therefore, in light of the above, low-GI carbohydrates are characterized by low postprandial endogenous GIP levels and increased GLP-1 concentrations. This most likely happens because slowly digested low-GI carbohydrates bypass the upper intestinal K-cells producing GIP and reach the most distant L-cells producing GLP-1.

3.3. Extrapancreatic Effects of Incretins

The GIP and GLP-1 receptors are widely expressed in multiple tissues and cell types [44] and a large body of evidence describes a plethora of pleiotropic activities for incretins outside of Langerhans islets. Most of these effects have been reported in animal experiments, and their relevance in humans have not always been ascertained [45].

3.4. GLP-1: The “Good” Incretin

3.4.1. Body Weight Regulation

GLP-1 play a physiological control of body weight by reducing appetite and enhancing satiety. The exact mechanism of these effects is complex and not completely understood. Evidence has been accumulated to support roles for both central and peripheral GLP-1 in the regulation of energy balance.
Intravenous GLP-1 infusion decreases gastric emptying rate by means of afferent-mediated vagal central mechanisms [46]. The effect has been observed both in healthy human subjects [47] and in patients with type 2 diabetes [48] in a dose-dependent manner.
However, rather than primarily lowering gastrointestinal motor activity, GLP-1 mainly reduces appetite by affecting the brain regulating center’s function [49]. GLP-1 receptor is expressed in various brain areas consistent with regulation of appetite and satiety, and intracerebroventricularly administered GLP-1 strongly reduces short-term food intake in rats [50]. The afferent vagal nerve system is more likely a mediator of this central effect of GLP-1, as total subdiaphragmatic vagotomy attenuates the reduction in food intake induced by peripheral GLP-1 administration in rodents [51]. GLP-1 activity in the brain of peripheral GLP-1 could be mediated by afferent vagal nerve termini adjacent to L-cells and/or in the hepatoportal region [52].
In addition to effects on energy intake, GLP-1 may contribute to negative energy balance by increasing energy expenditure, as intracerebroventricular injection of GLP-1 increases thermogenesis from interscapular brown adipose tissue in mice [53].

3.4.2. Lipid Metabolism

Fat ingestion is a physiological strong stimulator of GLP-1 release in humans and rodents [54]. On the other hand, GLP-1 infusion improves postprandial lipidemia [55], most likely as a result of delayed gastric emptying and insulin-mediated inhibition of lipolysis. In addition, a reduced Apolipoprotein B48 (Apo-B48) synthesis seems to be implicated. Apo-B48 is the primary protein component of the chylomicrons (CM)—it is specifically distributed in small intestine-derived CM. Its bloodstream concentration during fasting is usually quite low [56]. In rats, intravenously administered GLP-1 inhibits Apo-B48 production, resulting in decreased release of triglycerides into the circulation after lipid containing meals [57]. Exendin-4, a long-acting GLP-1 analogue, directly inhibits the synthesis of Apo-B48 from hamster enterocytes [58]. In this sense, the eventual postprandial hyperlipidemia, postprandial hyperglycemia, metabolic syndrome and myocardial infarction may be monitored and assessed by analyzing and monitoring Apo-B48 protein.

3.4.3. White Adipose Tissue

Even though the presence of GLP-1 receptor (GLP-1R) in adipose tissue is controversial, GLP-1 exerts various effects at this level [59]. Both GLP-1 and exendin-4 stimulate insulin-mediated glucose uptake in isolated rat adipocytes [60].
GLP-1 robustly stimulates lipolysis in adipocytes isolated from abdominal fat of morbidly obese subjects [61], but not in subcutaneous abdominal fat of healthy volunteers [62]. Treatment with a GLP-1-producing adenovirus reduces fat mass, proinflammatory M1 macrophages and inflammatory cytokines in ob/ob mice, thus suggesting an anti-inflammatory action of GLP-1 in adipose tissue [63].

3.4.4. Cardiovascular System

The GLP-1R has been found in various cardiovascular tissues and many studies indicate that GLP-1 have a host of protective effects at this level, independently of nutrient homeostasis [63,64].
In particular, endothelial dysfunction is believed to be an important link between the postprandial state, atherosclerosis and cardiovascular disease. Even if postprandial vasodilatation is mediated by insulin-induced release of nitric oxide [65], it has been demonstrated that GLP-1 per se has direct beneficial effects on endothelium-dependent vasodilatation, particularly in the postprandial state [66]. GLP-1 has been shown to increase NO availability in a wide range of vascular beds [67] and to inhibit endothelin-1 production [68]. In vitro, GLP-1 induces endothelium-dependent vasodilation in preconstricted pulmonary arteries [69] and inhibits TNF-alpha-mediated PAI-1 induction in vascular endothelial cells, improving cell dysfunction [70]. Administration of GLP-1 improves endothelial function in salt-sensitive hypertensive rats [71]. Of great relevance, pharmacological levels of GLP-1 improves endothelial function in healthy individuals [72] as well as in type 2 diabetic patients with stable coronary artery disease [73].
GLP-1 or GLP-1 receptor agonists have demonstrated multiple beneficial actions on the heart. In rats, GLP-1 protects myocardium from ischemia [74] and improves the cardiac function in animals with congestive heart failure [75]. In humans, GLP-1 attenuates ischemic left ventricular dysfunction during stress echocardiography in patients with coronary artery disease [76] and improves left ventricular function in some studies of heart failure subjects [77].
In patients with type 2 diabetes [78], long-term treatment with GLP-1 analogs reduces blood pressure, an effect well observed before significant weight loss and potentially mediated by GLP-1’s natriuretic effect and/or by improved endothelial function.
Notably, three CV outcome studies showed a significant reduction in a three-point MACE using GLP-1 analogs: liraglutide in LEADER, semaglutide in SUSTAIN-6, and recently dulaglutide in REWIND [79,80,81].

3.4.5. Kidney

Intravenous GLP-1 infusion increases natriuresis in rats and humans [82], possibly via increased atrial natriuretic peptide secretion from the heart [83] or via increased expression of the Na+/H+ exchanger in renal tubules [84]. Since the GLP-1 receptor is expressed in the brush border microvilli of proximal renal tubules and glomerular endothelial cells, a direct modulation of Na+ handling by the kidney cannot be excluded.

3.5. GIP: The “Bad” Incretin

3.5.1. White Adipose Tissue

Animal and human studies report a physiological role for GIP in the nutrient uptake into adipose tissues and, therefore, in the pathogenesis of obesity [85,86].
GIP may increase fat storage directly by binding to its receptors on adipocytes and indirectly by potentiating insulin secretion, which notoriously induce a switch from lipolysis to lipogenesis in the adipose tissue.
The fundamental support for the role of GIP in obesity comes from studies on GIP receptor knockout mice, which, unlike control animals, are protected from obesity and insulin resistance in response to high fat or high-GI diets [87]. Moreover, in a mice model of partial reduction of GIP secretion, high-fat diet alleviated obesity and lessened the degree of insulin resistance, accompanied by higher fat oxidation and energy expenditure [88].
There is also evidence that GIP induces both in mice and human fat cells expression and release of inflammatory cytokines with possible relapse on insulin resistance [89,90,91].

3.5.2. Fatty Liver

Liraglutide, a GLP-1 analog, may improve liver fibrosis in non-alcoholic fatty liver disease [92]. On the contrary, increased postprandial release of GIP has be linked to unfavorable effects in this condition. In fact, in patients with NASH, GIP response correlated directly with hepatic steatosis, postprandial resistin, and free fatty acid (FFA) increase [93].

3.5.3. Vascular Responses

There is strong evidence that GIP increases splanchnic perfusion after a meal to enhance blood supply to the gut and optimize nutrient delivery to the liver [94,95]. GIP may also be involved in non-splanchnic arterial regulation, likely by producing endothelin-1 and nitric oxide, as suggested by studies using cultured human endothelial cells [96].
In mouse arteries, GIP induces the expression of the proatherogenic cytokine osteopontin, a key player in the pathogenesis of vascular disease, through the local release of endothelin-1 and activation of CREB (a transcription factor participating in the regulation of osteopontin expression) [97].
Additional support for an unfavorable vascular role for GIP comes from a large-scale genome-wide association meta-analysis reporting the correlation of a variant in the GIP gene with myocardial infarction [98].

4. Conclusions

Plenty of evidence indicates that cardiometabolic health is affected by the quality of carbohydrate present in foods. As indicated by several studies exploring the incretin response to isomaltulose, low-GI carbohydrates are characterized by low postprandial endogenous GIP levels and increased GLP-1 concentrations. This probably is due to the different timing of stimulation of k-cells and L-cells, depending on the different GI of the carbohydrates.
Based on their opposite extrapancreatic effects, GIP and GLP-1 may behave as the “yin and yang” and could represent the causal link between GI and health status.
Currently, there is a lack of clinical trials investigating the impact of low-GI foods on body weight, glucose homeostasis and cardiovascular risk [3]. Moreover, the observed effects in intervention studies, when present, are generally of small magnitude.
However, a potential role in health outcome is suggested by the positive experience with alpha-glucosidase inhibitors [99,100], which convert meals into low-GI meals by shifting the sucrose absorption from the jejunal to ileal intestine, thus enhancing GLP-1 secretion [101,102].
In conclusion, it is reasonable to assume that incretin hormones play a crucial role in the attainment of a wide range of health benefits, as associated to the quality of ingested carbohydrates.
Currently, there are several physiopathological suggestions, but few strong clinical data, supporting this intriguing hypothesis, which, however, in light of recent important clinical evidence on the cardiometabolic protection effects of GLP1 receptor agonists, certainly deserve the development of ad hoc clinical trials.

Author Contributions

All the authors contributed equally to both the writing and the final revision of this review.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Dehghan, M.; Mente, A.; Zhang, X.; Swaminathan, S.; Li, W.; Mohan, V.; Iqbal, R.; Kumar, R.; Wentzel-Viljoen, E.; Rosengren, A.; et al. Prospective Urban Rural Epidemiology (PURE) study investigators. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): A prospective cohort study. Lancet 2017, 390, 2050–2062. [Google Scholar] [CrossRef]
  2. Augustin, L.S.; Kendall, C.W.; Jenkins, D.J.; Willett, W.C.; Astrup, A.; Barclay, A.W.; Björck, I.; Brand-Miller, J.C.; Brighenti, F.; Buyken, A.E.; et al. Glycemic index, glycemic load and glycemic response: An International Scientific Consensus Summit from the International Carbohydrate Quality Consortium (ICQC). Nutr. Metab. Cardiovasc Dis. 2015, 25, 795–815. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Clar, C.; Al-Khudairy, L.; Loveman, E.; Kelly, S.A.; Hartley, L.; Flowers, N.; Germanò, R.; Frost, G.; Rees, K. Low glycaemic index diets for the prevention of cardiovascular disease. Cochrane Database Syst. Rev. 2017, 7, CD004467. [Google Scholar] [CrossRef] [PubMed]
  4. Fan, J.; Song, Y.; Wang, Y.; Hui, R.; Zhang, W. Dietary glycemic index, glycemic load, and risk of coronary heart disease, stroke, and stroke mortality: A systematic review with meta-analysis. PLoS ONE 2012, 7, e52182. [Google Scholar] [CrossRef] [PubMed]
  5. Barclay, A.W.; Petocz, P.; McMillan-Price, J.; Flood, V.M.; Prvan, T.; Mitchell, P.; Brand-Miller, J.C. Glycemic index, glycemic load, and chronic disease risk—A meta-analysis of observational studies. Am. J. Clin. Nutr. Mar. 2008, 87, 627–637. [Google Scholar] [CrossRef] [PubMed]
  6. Livesey, G.; Taylor, R.; Livesey, H.; Liu, S. Is there a dose response relation of dietary glycemic load to risk of type 2 diabetes? Metaanalysis of prospective cohort studies. Am. J. Clin. Nutr. 2013, 97, 584–596. [Google Scholar] [CrossRef] [PubMed]
  7. Slama, G.; Elgrably, F.; Kabir, M.; Rizkalla, S. Low glycemic index foods should play a role in improving overall glycemic control in type-1 and type-2 diabetic patients and, more specifically, in correcting excessive postprandial hyperglycemia. Nestle Nutr. Workshop Ser. Clin. Perform. Programme 2006, 11, 73–81. [Google Scholar] [CrossRef] [PubMed]
  8. Drucker, D.J. The biology of incretin hormones. Cell Metab. 2006, 3, 153–165. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  9. Szczuko, M.; Zapałowska-Chwyć, M.; Drozd, A.; Maciejewska, D.; Starczewski, A.; Wysokiński, P.; Stachowska, E. Changes in the IGF-1 and TNF-α synthesis pathways before and after three-month reduction diet with low glicemic index in women with PCOS. Ginekol. Pol. 2018, 89, 295–303. [Google Scholar] [CrossRef] [PubMed]
  10. Szczuko, M.; Zapalowska-Chwyć, M.; Drozd, R. A Low Glycemic Index Decreases Inflammation by Increasing the Concentration of Uric Acid and the Activity of Glutathione Peroxidase (GPx3) in Patients with Polycystic Ovary Syndrome (PCOS). Molecules 2019, 24, 1508. [Google Scholar] [CrossRef] [PubMed]
  11. Nauck, M.A.; Meier, J.J. Incretin hormones: Their role in health and disease. Diabetes Obes. Metab. 2018, 20 (Suppl. 1), 5–21. [Google Scholar] [CrossRef] [PubMed]
  12. Parker, H.E.; Reimann, F.; Gribble, F.M. Molecular mechanisms underlying nutrient-stimulated incretin secretion. Expert Rev. Mol. Med. 2010, 12, e1. [Google Scholar] [CrossRef] [PubMed]
  13. Nauck, M.A.; Bartels, E.; Orskov, C.; Ebert, R.; Creutzfeldt, W. Additive insulinotropic eff ects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7–36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. J. Clin. Endocrinol. Metab. 1993, 76, 912–917. [Google Scholar] [PubMed]
  14. Chaikomin, R.; Wu, K.L.; Doran, S.; Jones, K.L.; Smout, A.J.P.M.; Renooij, W.; Holloway, R.H.; Meyer, J.H.; Horowitz, M.; Rayner, C.K. Concurrent duodenal manometric and impedance recording to evaluate the effects of hyoscine on motility and flow events, glucose absorption, and incretin release. Am. J. Physiol. Gastrointest. Liver Physiol. 2007, 292, G1099–G1104. [Google Scholar] [CrossRef] [PubMed]
  15. Nauck, M.A.; Meier, J.J. The incretin effect in healthy individuals and those with type 2 diabetes: Physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol. 2016, 4, 525–536. [Google Scholar] [CrossRef]
  16. Nauck, M.A.; Kleine, N.; Ørskov, C.; Holst, J.J.; Willms, B.; Creutzfeldt, W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993, 36, 741–744. [Google Scholar] [CrossRef] [PubMed]
  17. Drucker, D.J. Glucagon-like peptides: Regulators of cell proliferation, differentiation, and apoptosis. Mol. Endocrinol. 2003, 17, 161–171. [Google Scholar] [CrossRef]
  18. O’Neil, C.E.; Zanovec, M.; Cho, S.S.; Nicklas, T.A. Whole grain and fiber consumption are associated with lower body weight measures in USadults: National Health and Nutrition Examination Survey 1999–2004. Nutr. Res. 2010, 30, 815–822. [Google Scholar] [CrossRef]
  19. Gonzalez-Anton, C.; Lopez-Millan, B.; Rico, M.C.; Sanchez-Rodriguez, E.; Ruiz-Lopez, M.D.; Gil, A.; Mesa, M.D. An enriched, cereal-based bread affects appetite ratings and glycemic, insulinemic, and gastrointestinal hormone responses in healthy adults in a randomized, controlled trial. J. Nutr. 2015, 145, 231–238. [Google Scholar] [CrossRef]
  20. Gonzalez-Anton, C.; Rico, M.; Sanchez-Rodriguez, E.; Ruiz-Lopez, M.D.; Gil, A.; Mesa, M.D. Glycemic responses, appetite ratings and gastrointestinal hormone responses of most common breads consumed in Spain. A randomized control trial in healthy humans. Nutrients 2015, 7, 4033–4053. [Google Scholar] [CrossRef]
  21. Eelderink, C.; Noort, M.W.J.; Sozer, N.; Koehorst, M.; Holst, J.J.; Deacon, C.F.; Rehfeld, J.F.; Poutanen, K.; Vonk, R.J.; Oudhuis, L.; et al. Difference in postprandial GLP-1 response despite similar glucose kinetics after consumption of wheat breads with different particle size in healthy men. Eur. J. Nutr. 2017, 56, 1063–1076. [Google Scholar] [CrossRef] [PubMed]
  22. Hartvigsen, M.L.; Gregersen, S.; Lærke, H.N.; Holst, J.J.; Bach Knudsen, K.E.; Hermansen, K. Effects of concentrated arabinoxylan and β-glucan compared with refined wheat and whole grain rye on glucose and appetite in subjects with the metabolic syndrome: A randomized study. Eur. J. Clin. Nutr. 2014, 68, 84–90. [Google Scholar] [CrossRef] [PubMed]
  23. Najjar, A.M.; Parsons, P.M.; Duncan, A.M.; Robinson, L.E.; Yada, R.Y.; Graham, T.E. The acute impact of ingestion of breads of varying composition on blood glucose, insulin and incretins following first and second meals. Br. J. Nutr. 2009, 101, 391–398. [Google Scholar] [CrossRef] [PubMed]
  24. Mofidi, A.; Ferraro, Z.M.; Stewart, K.A.; Tulk, H.M.; Robinson, L.E.; Duncan, A.M.; Graham, T.E. The acute impact of ingestion of sourdough and whole-grain breads on blood glucose, insulin, and incretins in overweight and obese men. J. Nutr. Metab. 2012, 2012, 184710. [Google Scholar] [CrossRef] [PubMed]
  25. Tolhurst, G.; Heffron, H.; Lam, Y.S.; Parker, H.E.; Habib, A.M.; Diakogiannaki, E.; Cameron, J.; Grosse, J.; Reimann, F.; Gribble, F.M. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2012, 61, 364–371. [Google Scholar] [CrossRef] [PubMed]
  26. Katsuma, S.; Hirasawa, A.; Tsujimoto, G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem. Biophys Res. Commun. 2005, 329, 386–390. [Google Scholar] [CrossRef] [PubMed]
  27. Thomas, C.; Gioiello, A.; Noriega, L.; Strehle, A.; Oury, J.; Rizzo, G.; Macchiarulo, A.; Yamamoto, H.; Mataki, C.; Pruzanski, M.; et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009, 10, 167–177. [Google Scholar] [CrossRef] [PubMed]
  28. Rafferty, E.P.; Wylie, A.R.; Hand, K.H.; Elliott, C.E.; Grieve, D.J.; Green, B.D. Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R-/- mice. Biol. Chem. 2011, 392, 539–546. [Google Scholar] [CrossRef]
  29. Siddiqui, I.R.; Furgala, B. Isolation and characterization of oligosaccharides from honey. J. Apic. Res. 1967, 6, 139–145. [Google Scholar] [CrossRef]
  30. Lina, B.A.R.; Jonker, D.; Kozianowski, G. Isomaltulose (Palatinose): A review of biological and toxicological studies. Food Chem. Toxicol. 2002, 40, 1375–1381. [Google Scholar] [CrossRef]
  31. Nakajima, Y. Manufacture and utilization of palatinose. Jpn. Soc. Starch Sci. 1988, 35, 131–139. (In Japanese) [Google Scholar] [CrossRef]
  32. Tonouchi, H.; Yamaji, T.; Uchida, M.; Koganei, M.; Sasayama, A.; Kaneko, T.; Urita, Y.; Okuno, M.; Suzuki, K.; Kashimura, J.; et al. Studies on absorption and metabolism of palatinose (isomaltulose) in rats. Br. J. Nutr. 2011, 105, 10–14. [Google Scholar] [CrossRef] [PubMed]
  33. Van Can, J.G.; Ijzerman, T.H.; van Loon, L.J.C.; Brouns, F.; Blaak, E.E. Reduced glycaemic and insulinaemic responses following isomaltulose ingestion: Implications for postprandial substrate use. Br. J. Nutr. 2009, 102, 1408–1413. [Google Scholar] [CrossRef] [PubMed]
  34. Holub, I.; Gostner, A.; Theis, S.; Nosek, L.; Kudlich, T.; Melcher, R.; Scheppach, W. Novel findings on the metabolic effects of the low glycaemic carbohydrate isomaltulose (Palatinose). Br. J. Nutr. 2010, 103, 1730–1737. [Google Scholar] [CrossRef] [PubMed]
  35. Tsuji, Y.; Yamada, K.; Hosoya, N.; Moriuchi, S. Digestion and absorption of sugar substitutes in rat small intestine. J. Nutr. Sci. Vitaminol. 1986, 32, 93–100. [Google Scholar] [CrossRef] [PubMed]
  36. Zeevi, D.; Korem, T.; Zmora, N.; Israeli, D.; Rothschild, D.; Weinberger, A.; Ben-Yacov, O.; Lador, D.; Avnit-Sagi, T.; Lotan-Pompan, M.; et al. Personalized nutrition by prediction of glycemic responses. Cell 2015, 163, 1079–1094. [Google Scholar] [CrossRef] [PubMed]
  37. Keyhani-Nejad, F.; Irmler, M.; Isken, F.; Wirth, E.K.; Beckers, J.; Birkenfeld, A.L.; Pfeiffer, A.F. Nutritional strategy to prevent fatty liver and insulin resistance independent of obesity by reducing glucose-dependent insulinotropic polypeptide responses in mice. Diabetologia 2015, 58, 374–383. [Google Scholar] [CrossRef]
  38. Hira, T.; Muramatsu, M.; Okuno, M.; Hara, H. GLP-1 secretion in response to oral and luminal palatinose (isomaltulose) in rats. J. Nutr. Sci. Vitaminol. 2011, 57, 30–35. [Google Scholar] [CrossRef]
  39. Maeda, A.; Miyagawa, J.; Miuchi, M.; Nagai, E.; Konishi, K.; Matsuo, T.; Tokuda, M.; Kusunoki, Y.; Ochi, H.; Murai, K.; et al. Effects of the naturally- occurring disaccharides, palatinose and sucrose, on incretin secretion in healthy non-obese subjects. J. Diabetes Investig. 2013, 4, 281–286. [Google Scholar] [CrossRef]
  40. Ang, M.; Linn, T. Comparison of the effects of slowly and rapidly absorbed carbohydrates on postprandial glucose metabolism in type 2 diabetes mellitus patients: A randomized trial. Am. J. Clin. Nutr. 2014, 100, 1059–1068. [Google Scholar] [CrossRef] [PubMed]
  41. Keyhani-Nejad, F.; Kemper, M.; Schueler, R.; Pivovarova, O.; Rudovich, N.; Pfeiffer, A.F. Effects of palatinose and sucrose intake on glucose metabolism and incretin secretion in subjects withtype 2 diabetes. Diabetes Care 2016, 39, e38–e39. [Google Scholar] [CrossRef]
  42. Keller, J.; Kahlhöfer, J.; Peter, A.; Bosy-Westphal, A. Effects of low versus high glycemic index sugar-sweetened beverages on postprandial vasodilatation and inactivity-induced impairment of glucose metabolism in healthy men. Nutrients 2016, 8, 802. [Google Scholar] [CrossRef] [PubMed]
  43. Kong, M.F.; Chapman, I.; Goble, E.; Wishart, J.; Wittert, G.; Morris, H.; Horowitz, M. Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects. Peptides 1999, 20, 545–551. [Google Scholar] [CrossRef]
  44. Holst, J.J.; Vilsboll, T.; Deacon, C.F. The incretin system and its role in type 2 diabetes mellitus. Mol. Cell. Endocrinol. 2009, 297, 127–136. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Yamada, Y.; Tsukiyama, K.; Sato, T.; Shimizu, T.; Fujita, H.; Narita, T. Novel extrapancreatic effects of incretin. J. Diabetes Investig. 2016, 7 (Suppl. 1), 76–79. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Imeryūz, N.; Yeğen, B.C.; Bozkurt, A.; Coskun, T.; Villanueva-Peñacarrillo, M.L.; Ulusoy, N.B. Glucagonlike peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am. J. Physiol. Gastrointest. Liver Physiol. 1997, 273, G920–G927. [Google Scholar] [CrossRef] [PubMed]
  47. Nauck, M.A.; Niedereichholz, U.; Ettler, R.; Holst, J.J.; Orskov, C.; Ritzel, R.; Schmiegel, W.H. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am. J. Physiol. Endocrinol. Metab. 1997, 273, E981–E988. [Google Scholar] [CrossRef] [PubMed]
  48. Meier, J.J.; Gallwitz, B.; Salmen, S.; Goetze, O.; Holst, J.J.; Schmidt, W.E.; Nauck, M.A. Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 2003, 88, 2719–2725. [Google Scholar] [CrossRef]
  49. Raun, K.; Jelsing, J.; Vrang, N.; Tang-Christensen, M.; Dahl, K.; Knudsen, L.B. The GLP-1 analog liraglutide activates brainstem and hypothalamic neurons involved in appetite regulation. Diabetes 2010, 59 (Suppl. 1), A159–A160. [Google Scholar]
  50. Tang-Christensen, M.; Larsen, P.J.; Göke, R.; Fink-Jensen, A.; Jessop, D.S.; Möller, M.; Sheikh, S.P. Central administration of GLP-1-(7–36) amide inhibits food and water intake in rats. Am. J. Physiol. 1996, 271, R848–R856. [Google Scholar] [CrossRef] [PubMed]
  51. Abbott, C.R.; Monteiro, M.; Small, C.J.; Sajedi, A.; Smith, K.L.; Parkinson, J.R.; Ghatei, M.A.; Bloom, S.R. The inhibitory effects of peripheral administration of peptide YY (3–36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res. 2005, 1044, 127–131. [Google Scholar] [CrossRef] [PubMed]
  52. Holst, J.J. Incretin hormones and the satiation signal. Int. J. Obes. 2013, 37, 1161–1168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. Lockie, S.H.; Heppner, K.M.; Chaudhary, N.; Chabenne, J.R.; Morgan, D.A.; Veyrat-Durebex, C.; Ananthakrishnan, G.; Rohner-Jeanrenaud, F.; Drucker, D.J.; DiMarchi, R.; et al. Direct control of brown adipose tissue thermogenesis by central nervous system glucagon-like peptide-1 receptor signaling. Diabetes 2012, 61, 2753–2762. [Google Scholar] [CrossRef] [PubMed]
  54. Kieffer, T.J.; Habener, J.F. The glucagon-like peptides. Endocr. Rev. 1999, 20, 876–913. [Google Scholar] [CrossRef] [PubMed]
  55. Meier, J.J.; Gethmann, A.; Götze, O.; Gallwitz, B.; Holst, J.J.; Schmidt, W.E.; Nauck, M.A. Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans. Diabetologia 2006, 49, 452–458. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. Otokozawa, S.; Ai, M.; Diffenderfer, M.R.; Asztalos, B.F.; Tanaka, A.; Lamon-Fava, S.; Schaefer, E.J. Fasting and postprandial apolipoprotein B-48 levels in healthy, obese, and hyperlipidemic subjects. Metabolism 2009, 58, 1536–1542. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  57. Qin, X.; Shen, H.; Liu, M.; Yang, Q.; Zheng, S.; Sabo, M.; D’Alessio, D.A.; Tso, P. GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats. Am. J. Physiol. Gastrointest. Liver Physiol. 2005, 288, G943–G949. [Google Scholar] [CrossRef] [PubMed]
  58. Hsieh, J.; Longuet, C.; Baker, C.L.; Qin, B.; Federico, L.M.; Drucker, D.J.; Adeli, K. The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice. Diabetologia 2010, 53, 552–561. [Google Scholar] [CrossRef] [PubMed]
  59. Cho, Y.M.; Fujita, Y.; Kieffer, T.J. Glucagon-like peptide-1: Glucose homeostasis and beyond. Annu. Rev. Physiol. 2014, 76, 535–559. [Google Scholar] [CrossRef] [PubMed]
  60. Sancho, V.; Trigo, M.V.; González, N.; Valverde, I.; Malaisse, W.J.; Villanueva-Peñacarrillo, M.L. Effects of glucagon-like peptide-1 and exendins on kinase activity, glucose transport and lipid metabolism in adipocytes from normal and type-2 diabetic rats. J. Mol. Endocrinol. 2005, 35, 27–38. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  61. Sancho, V.; Trigo, M.V.; Martín-Duce, A.; González, N.; Acitores, A.; Arnés, L.; Valverde, I.; Malaisse, W.J.; Villanueva-Peñacarrillo, M.L. Effect of GLP-1 on D-glucose transport, lipolysis and lipogenesis in adipocytes of obese subjects. Int. J. Mol. Med. 2006, 17, 1133–1137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  62. Bertin, E.; Arner, P.; Bolinder, J.; Hagstrom-Toft, E. Action of glucagon and glucagon-like peptide-1-(7–36) amide on lipolysis in human subcutaneous adipose tissue and skeletal muscle in vivo. J. Clin. Endocrinol. Metab. 2001, 86, 1229–1234. [Google Scholar] [PubMed]
  63. Lee, Y.S.; Park, M.S.; Choung, J.S.; Kim, S.S.; Oh, H.H.; Choi, C.S.; Ha, S.Y.; Kang, Y.; Kim, Y.; Jun, H.S. Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes. Diabetologia 2012, 55, 2456–2468. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  64. Inzucchi, S.E.; McGuire, D.K. New drugs for the treatment of diabetes: Part II: Incretin-based therapy and beyond. Circulation 2008, 117, 574–584. [Google Scholar] [CrossRef] [PubMed]
  65. Scherrer, U.; Randin, D.; Vollenweider, P.; Vollenweider, L.; Nicod, P. Nitric oxide release accounts for insulin’s vascular effects in humans. J. Clin. Investig. 1994, 94, 2511–2515. [Google Scholar] [CrossRef] [PubMed]
  66. Ceriello, A.; Esposito, K.; Testa, R.; Bonfigli, A.R.; Marra, M.; Giugliano, D. The Possible Protective Role of Glucagon-Like Peptide 1 on Endothelium During the Meal and Evidence for an “Endothelial Resistance” to Glucagon-Like Peptide 1 in Diabetes. Diabetes Care 2011, 34, 697–702. [Google Scholar] [CrossRef] [PubMed]
  67. Liu, L.; Liu, J.; Huang, Y. Protective effects of glucagon-like peptide 1 on endothelial function in hypertension. J. Cardiovasc Pharmacol. 2015, 65, 399–405. [Google Scholar] [CrossRef] [PubMed]
  68. Dai, Y.; Mehta, J.L.; Chen, M. Glucagon-like peptide-1 receptor agonist liraglutide inhibits endothelin-1 in endothelial cell by repressing nuclear factor-kappa B activation. Cardiovasc Drugs Ther. 2013, 27, 371–380. [Google Scholar] [CrossRef] [PubMed]
  69. Richter, G.; Feddersen, O.; Wagner, U.; Barth, P.; Goke, R.; Goke, B. GLP-1 stimulates secretion of macromolecules from airways and relaxes pulmonary artery. Am. J. Physiol. 1993, 265, L374–L381. [Google Scholar] [CrossRef]
  70. Liu, H.; Hu, Y.; Simpson, R.W.; Dear, A.E. Glucagon-like peptide-1 attenuates tumor necrosis factor-alpha-mediated induction of plasminogen activator inhibitor-1 expression. J. Endocrinol. 2008, 196, 57–65. [Google Scholar] [CrossRef]
  71. Yu, M.; Moreno, C.; Hoagland, K.M.; Dahly, A.; Ditter, K.; Mistry, M.; Roman, R.J. Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J. Hypertens. 2003, 21, 1125–1135. [Google Scholar] [CrossRef] [PubMed]
  72. Basu, A.; Charkoudian, N.; Schrage, W.; Rizza, R.A.; Basu, R.; Joyner, M.J. Beneficial effects of GLP-1 on endothelial function in humans: Dampening by glyburide but not by glimepiride. Am. J. Physiol. Endocrinol. Metab. 2007, 293, E1289–E1295. [Google Scholar] [CrossRef] [PubMed]
  73. Nyström, T.; Gutniak, M.K.; Zhang, Q.; Zhang, F.; Holst, J.J.; Ahrén, B.; Sjöholm, Å. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am. J. Physiol. Endocrinol. Metab. 2004, 287, E1209–E1215. [Google Scholar] [CrossRef] [PubMed]
  74. Bose, A.K.; Mocanu, M.M.; Carr, R.D.; Brand, C.L.; Yellon, D.M. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 2005, 54, 146–151. [Google Scholar] [CrossRef] [PubMed]
  75. Liu, Q.; Anderson, C.; Broyde, A.; Polizzi, C.; Fernandez, R.; Baron, A.; Parkes, D.G. Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure. Cardiovasc Diabetol. 2010, 9, 76. [Google Scholar] [CrossRef] [PubMed]
  76. Read, P.A.; Khan, F.Z.; Dutka, D.P. Cardioprotection against ischaemia induced by dobutamine stress using glucagon-like peptide-1 in patients with coronary artery disease. Heart 2012, 98, 408–413. [Google Scholar] [CrossRef] [PubMed]
  77. Sokos, G.G.; Nikolaidis, L.A.; Mankad, S.; Elahi, D.; Shannon, R.P. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J. Cardiac Fail. 2006, 12, 694–699. [Google Scholar] [CrossRef]
  78. Ussher, J.R.; Drucker, D.J. Cardiovascular biology of the incretin system. Endocr. Rev. 2012, 33, 187–215. [Google Scholar] [CrossRef]
  79. Marso, S.P.; Daniels, G.H.; Brown-Frandsen, K.; Kristensen, P.; Mann, J.F.; Nauck, M.A.; Nissen, S.E.; Pocock, S.; Poulter, N.R.; Ravn, L.S.; et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 2016, 375, 311–322. [Google Scholar] [CrossRef]
  80. Marso, S.P.; Bain, S.C.; Consoli, A.; Eliaschewitz, F.G.; Jódar, E.; Leiter, L.A.; Lingvay, I.; Rosenstock, J.; Seufert, J.; Warren, M.L.; et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 2016, 375, 1834–1844. [Google Scholar] [CrossRef]
  81. Gerstein, H.C.; Colhoun, H.M.; Dagenais, G.R.; Diaz, R.; Lakshmanan, M.; Pais, P.; Probstfield, J.; Riesmeyer, J.S.; Riddle, M.C.; Rydén, L.; et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): A double-blind, randomised placebo-controlled trial. Lancet 2019, 394, 121–130. [Google Scholar] [CrossRef]
  82. Yerram, P.; Whaley-Connell, A. Novel role for the incretins in blood pressure regulation. Curr. Opin. Nephrol. Hypertens. 2012, 21, 463–468. [Google Scholar] [CrossRef] [PubMed]
  83. Kim, M.; Platt, M.J.; Shibasaki, T.; Quaggin, S.E.; Backx, P.H.; Seino, S.; Simpson, J.A.; Drucker, D.J. GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat. Med. 2013, 19, 567–575. [Google Scholar] [CrossRef] [PubMed]
  84. Rieg, T.; Gerasimova, M.; Murray, F.; Masuda, T.; Tang, T.; Rose, M.; Drucker, D.J.; Vallon, V. Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. Am. J. Physiol. Ren. Physiol. 2012, 303, F963–F971. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  85. Getty-Kaushik, L.; Song, D.H.; Boylan, M.; Corkey, B.E.; Wolfe, M.M. Glucose-dependent insulinotropic polypeptide modulates adipocyte lipolysis and reesterification. Obesity 2006, 14, 1124–1131. [Google Scholar] [CrossRef] [PubMed]
  86. Asmar, M.; Simonsen, L.; Madsbad, S.; Stallknecht, B.; Holst, J.J.; Bülow, J. Glucose-dependent insulinotropic polypeptide may enhance fatty acid re-esterification in subcutaneous abdominal adipose tissue in lean humans. Diabetes 2010, 59, 2160–2163. [Google Scholar] [CrossRef] [PubMed]
  87. Isken, F.; Weickert, M.O.; Tschöp, M.H.; Nogueiras, R.; Möhlig, M.; Abdelrahman, A.; Klaus, S.; Thorens, B.; Pfeiffer, A.F. Metabolic effects of diets differing in glycaemic index depend on age and endogenous glucose-dependent insulinotrophic polypeptide in mice. Diabetologia 2009, 52, 2159–2168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  88. Nasteska, D.; Harada, N.; Suzuki, K.; Yamane, S.; Hamasaki, A.; Joo, E.; Iwasaki, K.; Shibue, K.; Harada, T.; Inagaki, N. Chronic reduction of GIP secretion alleviates obesity and insulin resistance under high-fat diet conditions. Diabetes 2014, 63, 2332–2343. [Google Scholar] [CrossRef]
  89. Timper, K.; Grisouard, J.; Sauter, N.S.; Herzog-Radimerski, T.; Dembinski, K.; Peterli, R.; Frey, D.M.; Zulewski, H.; Keller, U.; Müller, B.; et al. Glucose-dependent insulinotropic polypeptide induces cytokine expression, lipolysis, and insulin resistance in human adipocytes. Am. J. Physiol. Endocrinol. Metab. 2013, 304, E1–E13. [Google Scholar] [CrossRef]
  90. Ahlqvist, E.; Osmark, P.; Kuulasmaa, T.; Pilgaard, K.; Omar, B.; Brøns, C.; Kotova, O.; Zetterqvist, A.V.; Stancáková, A.; Jonsson, A.; et al. Link between GIP and osteopontin in adipose tissue and insulin resistance. Diabetes 2013, 62, 2088–2094. [Google Scholar] [CrossRef]
  91. Chen, S.; Chen, S.; Okahara, F.; Osaki, N.; Shimotoyodome, A. Increased GIP signaling induces adipose inflammation via a HIF-1alpha-dependent pathway and impairs insulin sensitivity in mice. Am. J. Physiol. Endocrinol. Metab. 2015, 308, E414–E425. [Google Scholar] [CrossRef] [PubMed]
  92. Kahal, H.; Kahal, H.; Abouda, G.; Rigby, A.S.; Coady, A.M.; Kilpatrick, E.S.; Atkin, S.L. Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease. Clin. Endocrinol. 2014, 81, 523–528. [Google Scholar] [CrossRef] [PubMed]
  93. Musso, G.; Gambino, R.; Pacini, G.; De Michieli, F.; Cassader, M. Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: Dysregulated enteroadipocyte axis as a novel feature of fatty liver. Am. J. Clin. Nutr. 2009, 89, 558–567. [Google Scholar] [CrossRef] [PubMed]
  94. Fara, J.W.; Salazar, A.M. Gastric inhibitory polypeptide increases mesenteric blood flow. Proc. Soc. Exp. Biol. Med. 1978, 158, 446–448. [Google Scholar] [CrossRef] [PubMed]
  95. Kogire, M.; Inoue, K.; Sumi, S.; Doi, R.; Yun, M.; Kaji, H.; Tobe, T. Effects of gastric inhibitory polypeptide and glucagon on portal venous and hepatic arterial flow in conscious dogs. Dig. Dis. Sci. 1992, 37, 1666–1670. [Google Scholar] [CrossRef] [PubMed]
  96. Ding, K.H.; Zhong, Q.; Isales, C.M. Glucose-dependent insulinotropic peptide stimulates thymidine incorporation in endothelial cells: Role of endothelin-1. Am. J. Physiol. Endocrinol. Metab. 2003, 285, E390–E396. [Google Scholar] [CrossRef]
  97. Berglund, L.M.; Lyssenko, V.; Ladenvall, C.; Kotova, O.; Edsfeldt, A.; Pilgaard, K.; Alkayyali, S.; Brøns, C.; Forsblom, C.; Jonsson, A.; et al. Glucose-dependent insulinotropic polypeptide stimulates osteopontin expression in the vasculature via endothelin-1 and CREB. Diabetes 2016, 65, 239–254. [Google Scholar] [CrossRef] [PubMed]
  98. Schunkert, H.; König, I.R.; Kathiresan, S.; Reilly, M.P.; Assimes, T.L.; Holm, H.; Preuss, M.; Stewart, A.F.; Barbalic, M.; Gieger, C.; et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat. Genet. 2011, 43, 333–338. [Google Scholar] [CrossRef]
  99. Chiasson, J.L.; Josse, R.G.; Gomis, R.; Hanefeld, M.; Karasik, A.; Laakso, M. Acarbose for prevention of type 2 diabetes mellitus: The STOP-NIDDM randomised trial. Lancet 2002, 359, 2072–2077. [Google Scholar] [CrossRef]
  100. Chiasson, J.L.; Josse, R.G.; Gomis, R.; Hanefeld, M.; Karasik, A.; Laakso, M. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: The STOP-NIDDM trial. JAMA 2003, 290, 486–494. [Google Scholar] [CrossRef]
  101. Qualmann, C.; Nauck, M.A.; Holst, J.J.; Ørskov, C.; Creutzfeldt, W. Glucagon-like peptide 1 (7–36 amide) secretion in response to luminal sucrose from the upper and lower gut. A study using α-glucosidase inhibition (acarbose). Scand. J. Gastroenterol. 1995, 30, 892–896. [Google Scholar] [CrossRef]
  102. Seifarth, C.; Bergmann, J.; Holst, J.J.; Ritzel, R.; Schmiegel, W.; Nauck, M.A. Prolonged and enhanced secretion of glucagon-like peptide 1 (7–36 amide) after oral sucrose due to alpha-glucosidase inhibition (acarbose) in type 2 diabetic patients. Diabetes Med. 1998, 15, 485–491. [Google Scholar] [CrossRef]

Share and Cite

MDPI and ACS Style

Salvatore, T.; Nevola, R.; Pafundi, P.C.; Monaco, L.; Ricozzi, C.; Imbriani, S.; Rinaldi, L.; Sasso, F.C. Incretin Hormones: The Link between Glycemic Index and Cardiometabolic Diseases. Nutrients 2019, 11, 1878. https://doi.org/10.3390/nu11081878

AMA Style

Salvatore T, Nevola R, Pafundi PC, Monaco L, Ricozzi C, Imbriani S, Rinaldi L, Sasso FC. Incretin Hormones: The Link between Glycemic Index and Cardiometabolic Diseases. Nutrients. 2019; 11(8):1878. https://doi.org/10.3390/nu11081878

Chicago/Turabian Style

Salvatore, Teresa, Riccardo Nevola, Pia Clara Pafundi, Lucio Monaco, Carmen Ricozzi, Simona Imbriani, Luca Rinaldi, and Ferdinando Carlo Sasso. 2019. "Incretin Hormones: The Link between Glycemic Index and Cardiometabolic Diseases" Nutrients 11, no. 8: 1878. https://doi.org/10.3390/nu11081878

APA Style

Salvatore, T., Nevola, R., Pafundi, P. C., Monaco, L., Ricozzi, C., Imbriani, S., Rinaldi, L., & Sasso, F. C. (2019). Incretin Hormones: The Link between Glycemic Index and Cardiometabolic Diseases. Nutrients, 11(8), 1878. https://doi.org/10.3390/nu11081878

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop