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Nutrients
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Protein Metabolism and Glucose Homeostasis
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Protein Metabolism and Glucose Homeostasis

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 July 2019) | Viewed by 53526

Special Issue Editor

Prof. Claire C. Gaudichon

E-Mail Website
Guest Editor
UMR PNCA, AgroParisTech, INRA, Université Paris Saclay, 16 Rue Claude Bernard, 75005, Paris, France
Interests: Protein metabolism, protein digestion, gluconeogenesis, stable isotopes

Special Issue Information

Dear Colleagues,

Glucose homeostasis is under the control of multiple factors linked to genetics and lifestyle. Dietary factors are important determinants of glucose metabolism, and, among them, protein intake is involved in short- and long-term effects. Direct mechanisms include regulatory effects of amino acids on pancreatic, gastrointestinal, and hepatic hormone secretion, the role of amino acids as precursors and signals in the different glucose metabolism pathways, as well as their interference with insulin signaling. Indirect effects of dietary protein on glucose homeostasis must also be considered, since the level and sources of proteins influence the diet composition with respect to other nutrients and non-nutritive molecules.

This Special Issue aims to gather recent advances in the understanding of the interferences between protein metabolism and glucose homeostasis, their dysregulations and related pathologies, and of how the quantity and quality of dietary protein positively or negatively influence related health outcomes. Reviews, experimental works in animals and humans, as well as epidemiological studies are welcome.

Prof. Claire C. Gaudichon
Guest Editor

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Keywords

  • dietary protein 
  • amino acids
  • gluconeogenesis
  • diabetes
  • insulin resistance
  • incretins

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Published Papers (5 papers)

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Research

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16 pages, 806 KiB  
Article
Plasma Free Amino Acid Responses to Whey Protein and Their Relationships with Gastric Emptying, Blood Glucose- and Appetite-Regulatory Hormones and Energy Intake in Lean Healthy Men
by Rachel A. Elovaris, Amy T. Hutchison, Kylie Lange, Michael Horowitz, Christine Feinle-Bisset and Natalie D. Luscombe-Marsh
Nutrients 2019, 11(10), 2465; https://doi.org/10.3390/nu11102465 - 15 Oct 2019
Cited by 19 | Viewed by 4016
Abstract
This study determined the effects of increasing loads of whey protein on plasma amino acid (AA) concentrations, and their relationships with gastric emptying, blood glucose- and appetite-regulatory hormones, blood glucose and energy intake. Eighteen healthy lean men participated in a double-blinded study, in [...] Read more.
This study determined the effects of increasing loads of whey protein on plasma amino acid (AA) concentrations, and their relationships with gastric emptying, blood glucose- and appetite-regulatory hormones, blood glucose and energy intake. Eighteen healthy lean men participated in a double-blinded study, in which they consumed, on 3 separate occasions, in randomised order, 450-mL drinks containing either 30 g (L) or 70 g (H) of pure whey protein isolate, or control with 0 g of protein (C). Gastric emptying, serum concentrations of AAs, ghrelin, cholecystokinin (CCK), glucagon-like-peptide 1 (GLP-1), insulin, glucagon and blood glucose were measured before and after the drinks over 180 min. Then energy intake was quantified. All AAs were increased, and 7/20 AAs were increased more by H than L. Incremental areas under the curve (iAUC0–180 min) for CCK, GLP-1, insulin and glucagon were correlated positively with iAUCs of 19/20 AAs (p < 0.05). The strongest correlations were with the branched-chain AAs as well as lysine, tyrosine, methionine, tryptophan, and aspartic acid (all R2 > 0.52, p < 0.05). Blood glucose did not correlate with any AA (all p > 0.05). Ghrelin and energy intake correlated inversely, but only weakly, with 15/20 AAs (all R2 < 0.34, p < 0.05). There is a strong relationship between gluco-regulatory hormones with a number of (predominantly essential) AAs. However, the factors mediating the effects of protein on blood glucose and energy intake are likely to be multifactorial. Full article
(This article belongs to the Special Issue Protein Metabolism and Glucose Homeostasis)
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11 pages, 446 KiB  
Article
Obesity Status Affects the Relationship Between Protein Intake and Insulin Sensitivity in Late Pregnancy
by Brittany R. Allman, Eva Diaz Fuentes, D. Keith Williams, Donald E. Turner, Aline Andres and Elisabet Børsheim
Nutrients 2019, 11(9), 2190; https://doi.org/10.3390/nu11092190 - 11 Sep 2019
Cited by 7 | Viewed by 3706
Abstract
The purpose of this study was to determine the associations between amount and type of dietary protein intake and insulin sensitivity in late pregnancy, in normal weight and overweight women (29.8 ± 0.2 weeks gestation, n = 173). A 100-g oral glucose tolerance [...] Read more.
The purpose of this study was to determine the associations between amount and type of dietary protein intake and insulin sensitivity in late pregnancy, in normal weight and overweight women (29.8 ± 0.2 weeks gestation, n = 173). A 100-g oral glucose tolerance test (OGTT) was administered following an overnight fast to estimate the metabolic clearance rate of glucose (MCR, mg·kg−1·min−1) using four different equations accounting for the availability of blood samples. Total (TP), animal (AP), and plant (PP) protein intakes were assessed using a 3-day food record. Two linear models with MCR as the response variable were fitted to the data to estimate the relationship of protein intake to insulin sensitivity either unadjusted or adjusted for early pregnancy body mass index (BMI) because of the potential of BMI to influence this relationship. There was a positive association between TP (β = 1.37, p = 0.002) and PP (β = 4.44, p < 0.001) intake in the last trimester of pregnancy and insulin sensitivity that weakened when accounting for early pregnancy BMI. However, there was no relationship between AP intake and insulin sensitivity (β = 0.95, p = 0.08). Therefore, early pregnancy BMI may be a better predictor of insulin sensitivity than dietary protein intake in late pregnancy. Full article
(This article belongs to the Special Issue Protein Metabolism and Glucose Homeostasis)
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12 pages, 726 KiB  
Article
Identification of the Secreted Proteins Originated from Primary Human Hepatocytes and HepG2 Cells
by Andras Franko, Sonja Hartwig, Jörg Kotzka, Marc Ruoß, Andreas K. Nüssler, Alfred Königsrainer, Hans-Ulrich Häring, Stefan Lehr and Andreas Peter
Nutrients 2019, 11(8), 1795; https://doi.org/10.3390/nu11081795 - 3 Aug 2019
Cited by 25 | Viewed by 4953
Abstract
The liver plays a pivotal role in whole-body carbohydrate, lipid, and protein metabolism. One of the key regulators of glucose and lipid metabolism are hepatokines, which are found among the liver secreted proteins, defined as liver secretome. To elucidate the composition of the [...] Read more.
The liver plays a pivotal role in whole-body carbohydrate, lipid, and protein metabolism. One of the key regulators of glucose and lipid metabolism are hepatokines, which are found among the liver secreted proteins, defined as liver secretome. To elucidate the composition of the human liver secretome and identify hepatokines in primary human hepatocytes (PHH), we conducted comprehensive protein profiling on conditioned medium (CM) of PHH. Secretome profiling using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) identified 691 potential hepatokines in PHH. Subsequently, pathway analysis assigned these proteins to acute phase response, coagulation, and complement system pathways. The secretome of PHH was compared to the secreted proteins of the liver hepatoma cell line HepG2. Although the secretome of PHH and HepG2 cells show a high overlap, the HepG2 secretome rather mirrors the fetal liver with some cancer characteristics. Collectively, our study represents one of the most comprehensive secretome profiling approaches for PHH, allowing new insights into the composition of the secretome derived from primary human material, and points out strength and weakness of using HepG2 cell secretome as a model for the analysis of the human liver secretome. Full article
(This article belongs to the Special Issue Protein Metabolism and Glucose Homeostasis)
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15 pages, 842 KiB  
Article
Non-Alcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: Role of Circulating Branched-Chain Amino Acids
by Eline H. van den Berg, Jose L. Flores-Guerrero, Eke G. Gruppen, Martin H. de Borst, Justyna Wolak-Dinsmore, Margery A. Connelly, Stephan J. L. Bakker and Robin P. F. Dullaart
Nutrients 2019, 11(3), 705; https://doi.org/10.3390/nu11030705 - 26 Mar 2019
Cited by 64 | Viewed by 6984
Abstract
Non-alcoholic fatty liver disease (NAFLD) is likely to be associated with elevated plasma branched-chain amino acids (BCAAs) and may precede the development of type 2 diabetes (T2D). We hypothesized that BCAAs may be involved in the pathogenesis of T2D attributable to NAFLD and [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is likely to be associated with elevated plasma branched-chain amino acids (BCAAs) and may precede the development of type 2 diabetes (T2D). We hypothesized that BCAAs may be involved in the pathogenesis of T2D attributable to NAFLD and determined the extent to which plasma BCAAs influence T2D development in NAFLD. We evaluated cross-sectional associations of NAFLD with fasting plasma BCAAs (nuclear magnetic resonance spectroscopy), and prospectively determined the extent to which the influence of NAFLD on incident T2D is attributable to BCAA elevations. In the current study, 5791 Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort participants without T2D at baseline were included. Elevated fatty liver index (FLI) ≥60, an algorithm based on triglycerides, gamma-glutamyltransferase, body mass index (BMI) and waist circumference, was used as proxy of NAFLD. Elevated FLI ≥ 60 was present in 1671 (28.9%) participants. Cross-sectionally, BCAAs were positively associated with FLI ≥ 60 (β = 0.208, p < 0.001). During a median follow-up of 7.3 years, 276 participants developed T2D, of which 194 (70.2%) had an FLI ≥ 60 (log-rank test, p < 0.001). Cox regression analyses revealed that both FLI ≥60 (hazard ratio (HR) 3.46, 95% CI 2.45–4.87, p < 0.001) and higher BCAA levels (HR 1.19, 95% CI 1.03–1.37, p = 0.01) were positively associated with incident T2D. Mediation analysis showed that the association of FLI with incident T2D was in part attributable to elevated BCAAs (proportion mediated 19.6%). In conclusion, both elevated FLI and elevated plasma BCAA levels are associated with risk of incident T2D. The association of NAFLD with T2D development seems partly mediated by elevated BCAAs. Full article
(This article belongs to the Special Issue Protein Metabolism and Glucose Homeostasis)
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Review

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28 pages, 1642 KiB  
Review
Glycine Metabolism and Its Alterations in Obesity and Metabolic Diseases
by Anaïs Alves, Arthur Bassot, Anne-Laure Bulteau, Luciano Pirola and Béatrice Morio
Nutrients 2019, 11(6), 1356; https://doi.org/10.3390/nu11061356 - 16 Jun 2019
Cited by 222 | Viewed by 32645
Abstract
Glycine is the proteinogenic amino-acid of lowest molecular weight, harboring a hydrogen atom as a side-chain. In addition to being a building-block for proteins, glycine is also required for multiple metabolic pathways, such as glutathione synthesis and regulation of one-carbon metabolism. Although generally [...] Read more.
Glycine is the proteinogenic amino-acid of lowest molecular weight, harboring a hydrogen atom as a side-chain. In addition to being a building-block for proteins, glycine is also required for multiple metabolic pathways, such as glutathione synthesis and regulation of one-carbon metabolism. Although generally viewed as a non-essential amino-acid, because it can be endogenously synthesized to a certain extent, glycine has also been suggested as a conditionally essential amino acid. In metabolic disorders associated with obesity, type 2 diabetes (T2DM), and non-alcoholic fatty liver disease (NAFLDs), lower circulating glycine levels have been consistently observed, and clinical studies suggest the existence of beneficial effects induced by glycine supplementation. The present review aims at synthesizing the recent advances in glycine metabolism, pinpointing its main metabolic pathways, identifying the causes leading to glycine deficiency—especially in obesity and associated metabolic disorders—and evaluating the potential benefits of increasing glycine availability to curb the progression of obesity and obesity-related metabolic disturbances. This study focuses on the importance of diet, gut microbiota, and liver metabolism in determining glycine availability in obesity and associated metabolic disorders. Full article
(This article belongs to the Special Issue Protein Metabolism and Glucose Homeostasis)
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