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The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 51594

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Prof. Dr. Kazumi Yagasaki

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Guest Editor

Division of Applied Biological Chemistry, Institute of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan
Interests: pharmacology; bromacology (=food pharmacology) (cf. bromacology is our neologism); functional foods; biofactors; nutrients; non-nutrients; phytochemicals; zoochemicals; amino acids (BCAA); fatty acids; diabetes; hyperglycemia; hyperuricemia; dyslipidemia; nephritis; hepatoma; animal cell technology; cultured cells; animal model; signaling pathway; transporter, receptor; AMPK; Akt; PKC; GLUT4 etc
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Prof. Dr. Christo J.F. Muller

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Co-Guest Editor

1. Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg 7505, South Africa
2. Centre for Cardiometabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa
3. Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3880, South Africa
Interests: metabolic disease (pathophysiology, prevention and treatment); phytotherapeutics and early detection of type 2 diabetes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diabetes, especially global prevalence of type 2 diabetes (T2D), is increasing as reported in the Diabetes Atlas, 9th edition, (International Diabetes Federation, 2019). In 2019, it is estimates that 463 million people have diabetes, and this number is projected to reach 578 million by 2030, and 700 million by 2045. Natural products from terrestrial and aquatic organisms still constitute huge sources of biologically active factors for the development of drugs, cosmetics or nutraceuticals as well as our daily foods. Screening antidiabetic components from edible natural products and clarifying their modes of actions are considered to be an intelligent policy from the aspects of safety and diabetes prevention, because they have long histories of ingestion every day. This issue expects recent studies on preventive and/or alleviating effects of various biofactors against diabetes, especially type 2 diabetes (T2D), and diabetes related disorders as well as those on their modes of actions at molecular, cellular, tissue and/or whole-body levels. In this issue, biofactors include both non-nutrients such as various phytochemicals and nutrients, for example, branched-chain amino acids (BCAA), peptides and lipids.

Prof. Kazumi Yagasaki
Guest Editor

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Keywords

diabetes
type 2 diabetes (T2D)
insulin resistance
myocytes
adipocytes
pancreatic β cells
T2D model animal
cellular signaling
Akt
AMPK
GLUTs
microarray
phytochemicals
zoochemicals
BCAAs

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 176 KiB

Open AccessEditorial

The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes

by Kazumi Yagasaki and Christo J. F. Muller

Int. J. Mol. Sci. 2022, 23(14), 7765; https://doi.org/10.3390/ijms23147765 - 14 Jul 2022

Cited by 5 | Viewed by 1948

Abstract

There are three main types of diabetes, namely, type 1 diabetes, type 2 diabetes (T2D), and diabetes in pregnancy (gestational diabetes) [...] Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

Research

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22 pages, 4049 KiB

Open AccessArticle

Anti-Obesity and Anti-Hyperglycemic Effects of Meretrix lusoria Protamex Hydrolysate in ob/ob Mice

by Min Ju Kim, Ramakrishna Chilakala, Hee Geun Jo, Seung-Jae Lee, Dong-Sung Lee and Sun Hee Cheong

Int. J. Mol. Sci. 2022, 23(7), 4015; https://doi.org/10.3390/ijms23074015 - 5 Apr 2022

Cited by 14 | Viewed by 3270

Abstract

Meretrix lusoria (M. lusoria) is an economically important shellfish which is widely distributed in South Eastern Asia that contains bioactive peptides, proteins, and enzymes. In the present study, the extracted meat content of M. lusoria was enzymatic hydrolyzed using four different commercial proteases (neutrase, protamex, alcalase, and flavourzyme). Among the enzymatic hydrolysates, M. lusoria protamex hydrolysate (MLPH) fraction with MW ≤ 1 kDa exhibited the highest free radical scavenging ability. The MLPH fraction was further purified and an amino acid sequence (KDLEL, 617.35 Da) was identified by LC-MS/MS analysis. The purpose of this study was to investigate the anti-obesity and anti-hyperglycemic effects of MLPH containing antioxidant peptides using ob/ob mice. Treatment with MLPH for 6 weeks reduced body and organ weight and ameliorated the effects of hepatic steatosis and epididymal fat, including a constructive effect on hepatic and serum marker parameters. Moreover, hepatic antioxidant enzyme activities were upregulated and impaired glucose tolerance was improved in obese control mice. In addition, MLPH treatment markedly suppressed mRNA expression related to lipogenesis and hyperglycemia through activation of AMPK phosphorylation. These findings suggest that MLPH has anti-obesity and anti-hyperglycemic potential and could be effectively applied as a functional food ingredient or pharmaceutical. Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

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22 pages, 3967 KiB

Open AccessArticle

Capsaicin and Zinc Promote Glucose Uptake in C2C12 Skeletal Muscle Cells through a Common Calcium Signalling Pathway

by Parisa Vahidi Ferdowsi, Kiran D. K. Ahuja, Jeffrey M. Beckett and Stephen Myers

Int. J. Mol. Sci. 2022, 23(4), 2207; https://doi.org/10.3390/ijms23042207 - 17 Feb 2022

Cited by 7 | Viewed by 3397

Abstract

Capsaicin and zinc have recently been highlighted as potential treatments for glucose metabolism disorders; however, the effect of these two natural compounds on signalling pathways involved in glucose metabolism is still uncertain. In this study, we assessed the capsaicin- or zinc- induced activation of signalling molecules including calcium/calmodulin-dependent protein kinase 2 (CAMKK2), cAMP-response element-binding protein (CREB), and target of rapamycin kinase complex 1 (TORC1). Moreover, the expression status of genes associated with the control of glucose metabolism was measured in treated cells. The activation of cell signalling proteins was then evaluated in capsaicin- or zinc treated cells in the presence or absence of cell-permeant calcium chelator (BAPTA-AM) and the CAMKK inhibitor (STO-609). Finally, capsaicin- and zinc-induced glucose uptake was measured in the cells pre-treated with or without BAPTA-AM. Our results indicate that calcium flux induced by capsaicin or zinc led to activation of calcium signalling molecules and promoting glucose uptake in skeletal muscle cells. Pharmacological inhibition of CAMKK diminished activation of signalling molecules. Moreover, we observed an increase in intracellular cAMP levels in the cells after treatment with capsaicin and zinc. Our data show that capsaicin and zinc mediate glucose uptake in C2C12 skeletal muscle cells through the activation of calcium signalling. Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

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11 pages, 1926 KiB

Open AccessArticle

Effects of Baccharin Isolated from Brazilian Green Propolis on Adipocyte Differentiation and Hyperglycemia in ob/ob Diabetic Mice

by Akio Watanabe, Marília Oliveira de Almeida, Yusuke Deguchi, Ryuzo Kozuka, Caroline Arruda, Andresa Aparecida Berreta, Jairo Kenupp Bastos, Je-Tae Woo and Takayuki Yonezawa

Int. J. Mol. Sci. 2021, 22(13), 6954; https://doi.org/10.3390/ijms22136954 - 28 Jun 2021

Cited by 6 | Viewed by 3410

Abstract

Propolis is a honeybee product with various biological activities, including antidiabetic effects. We previously reported that artepillin C, a prenylated cinnamic acid derivative isolated from Brazilian green propolis, acts as a peroxisome proliferator-activated receptor γ (PPARγ) ligand and promotes adipocyte differentiation. In this study, we examined the effect of baccharin, another major component of Brazilian green propolis, on adipocyte differentiation. The treatment of mouse 3T3-L1 preadipocytes with baccharin resulted in increased lipid accumulation, cellular triglyceride levels, glycerol-3-phosphate dehydrogenase activity, and glucose uptake. The mRNA expression levels of PPARγ and its target genes were also increased by baccharin treatment. Furthermore, baccharin enhanced PPARγ-dependent luciferase activity, suggesting that baccharin promotes adipocyte differentiation via PPARγ activation. In diabetic ob/ob mice, intraperitoneal administration of 50 mg/kg baccharin significantly improved blood glucose levels. Our results suggest that baccharin has a hypoglycemic effect on glucose metabolic disorders, such as type 2 diabetes mellitus. Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

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19 pages, 20621 KiB

Open AccessArticle

Isoprenoid Derivatives of Lysophosphatidylcholines Enhance Insulin and GLP-1 Secretion through Lipid-Binding GPCRs

by Anna Drzazga, Daria Kamińska, Anna Gliszczyńska and Edyta Gendaszewska-Darmach

Int. J. Mol. Sci. 2021, 22(11), 5748; https://doi.org/10.3390/ijms22115748 - 27 May 2021

Cited by 8 | Viewed by 4152

Abstract

Insulin plays a significant role in carbohydrate homeostasis as the blood glucose lowering hormone. Glucose-induced insulin secretion (GSIS) is augmented by glucagon-like peptide (GLP-1), a gastrointestinal peptide released in response to ingesting nutriments. The secretion of insulin and GLP-1 is mediated by the binding of nutrients to G protein-coupled receptors (GPCRs) expressed by pancreatic β-cells and enteroendocrine cells, respectively. Therefore, insulin secretagogues and incretin mimetics currently serve as antidiabetic treatments. This study demonstrates the potency of synthetic isoprenoid derivatives of lysophosphatidylcholines (LPCs) to stimulate GSIS and GLP-1 release. Murine insulinoma cell line (MIN6) and enteroendocrinal L cells (GLUTag) were incubated with LPCs bearing geranic acid (1-GA-LPC), citronellic acid (1-CA-LPC), 3,7-dimethyl-3-vinyloct-6-enoic acid (GERA-LPC), and (E)-3,7,11-trimethyl- 3-vinyldodeca-6,10-dienoic acid (1-FARA-LPC). Respective free terpene acids were also tested for comparison. Besides their insulin- and GLP-1-secreting capabilities, we also investigated the cytotoxicity of tested compounds, the ability to intracellular calcium ion mobilization, and targeted GPCRs involved in maintaining lipid and carbohydrate homeostasis. We observed the high cytotoxicity of 1-GERA-LPC and 1-FARA-LPC in contrast 1-CA-LPC and 1-GA-LPC. Moreover, 1-CA-LPC and 1-GA-LPC demonstrated the stimulatory effect on GSIS and 1-CA-LPC augmented GLP-1 secretion. Insulin and GLP-1 release appeared to be GPR40-, GPR55-, GPR119- and GPR120-dependent. Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

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Review

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25 pages, 2157 KiB

Open AccessReview

Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways

by Feten Zar Kalai, Mondher Boulaaba, Farhana Ferdousi and Hiroko Isoda

Int. J. Mol. Sci. 2022, 23(2), 704; https://doi.org/10.3390/ijms23020704 - 9 Jan 2022

Cited by 37 | Viewed by 5289

Abstract

Diabetes mellitus, especially type 2 (T2DM), is a major public health problem globally. DM is characterized by high levels of glycemia and insulinemia due to impaired insulin secretion and insulin sensitivity of the cells, known as insulin resistance. T2DM causes multiple and severe complications such as nephropathy, neuropathy, and retinopathy causing cell oxidative damages in different internal tissues, particularly the pancreas, heart, adipose tissue, liver, and kidneys. Plant extracts and their bioactive phytochemicals are gaining interest as new therapeutic and preventive alternatives for T2DM and its associated complications. In this regard, isorhamnetin, a plant flavonoid, has long been studied for its potential anti-diabetic effects. This review describes its impact on reducing diabetes-related disorders by decreasing glucose levels, ameliorating the oxidative status, alleviating inflammation, and modulating lipid metabolism and adipocyte differentiation by regulating involved signaling pathways reported in the in vitro and in vivo studies. Additionally, we include a post hoc whole-genome transcriptome analysis of biological activities of isorhamnetin using a stem cell-based tool. Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

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22 pages, 2047 KiB

Open AccessReview

New Insights into the Efficacy of Aspalathin and Other Related Phytochemicals in Type 2 Diabetes—A Review

by Christo J. F. Muller, Elizabeth Joubert, Nireshni Chellan, Yutaka Miura and Kazumi Yagasaki

Int. J. Mol. Sci. 2022, 23(1), 356; https://doi.org/10.3390/ijms23010356 - 29 Dec 2021

Cited by 14 | Viewed by 4475

Abstract

In the pursuit of bioactive phytochemicals as a therapeutic strategy to manage metabolic risk factors for type 2 diabetes (T2D), aspalathin, C-glucosyl dihydrochalcone from rooibos (Aspalathus linearis), has received much attention, along with its C-glucosyl flavone derivatives and phlorizin, the apple O-glucosyl dihydrochalcone well-known for its antidiabetic properties. We provided context for dietary exposure by highlighting dietary sources, compound stability during processing, bioavailability and microbial biotransformation. The review covered the role of these compounds in attenuating insulin resistance and enhancing glucose metabolism, alleviating gut dysbiosis and associated oxidative stress and inflammation, and hyperuricemia associated with T2D, focusing largely on the literature of the past 5 years. A key focus of this review was on emerging targets in the management of T2D, as highlighted in the recent literature, including enhancing of the insulin receptor and insulin receptor substrate 1 signaling via protein tyrosine phosphatase inhibition, increasing glycolysis with suppression of gluconeogenesis by sirtuin modulation, and reducing renal glucose reabsorption via sodium-glucose co-transporter 2. We conclude that biotransformation in the gut is most likely responsible for enhancing therapeutic effects observed for the C-glycosyl parent compounds, including aspalathin, and that these compounds and their derivatives have the potential to regulate multiple factors associated with the development and progression of T2D. Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

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23 pages, 2680 KiB

Open AccessReview

Effectiveness of Magnolol, a Lignan from Magnolia Bark, in Diabetes, Its Complications and Comorbidities—A Review

by Katarzyna Szałabska-Rąpała, Weronika Borymska and Ilona Kaczmarczyk-Sedlak

Int. J. Mol. Sci. 2021, 22(18), 10050; https://doi.org/10.3390/ijms221810050 - 17 Sep 2021

Cited by 25 | Viewed by 7128

Abstract

Diabetes mellitus is a chronic metabolic disease characterized by disturbances in carbohydrate, protein, and lipid metabolism, often accompanied by oxidative stress. Diabetes treatment is a complicated process in which, in addition to the standard pharmacological action, it is necessary to append a comprehensive approach. Introducing the aspect of non-pharmacological treatment of diabetes allows one to alleviate its many adverse complications. Therefore, it seems important to look for substances that, when included in the daily diet, can improve diabetic parameters. Magnolol, a polyphenolic compound found in magnolia bark, is known for its health-promoting activities and multidirectional beneficial effects on the body. Accordingly, the goal of this review is to systematize the available scientific literature on its beneficial effects on type 2 diabetes and its complications. Taking the above into consideration, the article collects data on the favorable effects of magnolol on parameters related to glycemia, lipid metabolism, or oxidative stress in the course of diabetes. After careful analysis of many scientific articles, it can be concluded that this lignan is a promising agent supporting the conventional therapies with antidiabetic drugs in order to manage diabetes and diabetes-related diseases. Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

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15 pages, 697 KiB

Open AccessReview

Improvement of Glucose Tolerance by Food Factors Having Glucagon-Like Peptide-1 Releasing Activity

by Tohru Hira, Aphichat Trakooncharoenvit, Hayate Taguchi and Hiroshi Hara

Int. J. Mol. Sci. 2021, 22(12), 6623; https://doi.org/10.3390/ijms22126623 - 21 Jun 2021

Cited by 17 | Viewed by 10219

Abstract

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone released from enteroendocrine L cells in response to meal ingestion. GLP-1 receptor agonists and GLP-1 enhancers have been clinically employed to treat diabetes owing to their glucose-dependent insulin-releasing activity. The release of GLP-1 is primarily stimulated by macronutrients such as glucose and fatty acids, which are nutritionally indispensable; however, excessive intake of sugar and fat is responsible for the development of obesity and diabetes. Therefore, GLP-1 releasing food factors, such as dietary peptides and non-nutrients, are deemed desirable for improving glucose tolerance. Human and animal studies have revealed that dietary proteins/peptides have a potent effect on stimulating GLP-1 secretion. Studies in enteroendocrine cell models have shown that dietary peptides, amino acids, and phytochemicals, such as quercetin, can directly stimulate GLP-1 secretion. In our animal experiments, these food factors improved glucose metabolism and increased GLP-1 secretion. Furthermore, some dietary peptides not only stimulated GLP-1 secretion but also reduced plasma peptidase activity, which is responsible for GLP-1 inactivation. Herein, we review the relationship between GLP-1 and food factors, especially dietary peptides and flavonoids. Accordingly, utilization of food factors with GLP-1-releasing/enhancing activity is a promising strategy for preventing and treating obesity and diabetes. Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

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20 pages, 1855 KiB

Open AccessReview

Activation of Insulin Signaling by Botanical Products

by Tovit Rosenzweig and Sanford R. Sampson

Int. J. Mol. Sci. 2021, 22(8), 4193; https://doi.org/10.3390/ijms22084193 - 18 Apr 2021

Cited by 9 | Viewed by 5095

Abstract

Type 2 diabetes (T2D) is a worldwide health problem, ranked as one of the leading causes for severe morbidity and premature mortality in modern society. Management of blood glucose is of major importance in order to limit the severe outcomes of the disease. However, despite the impressive success in the development of new antidiabetic drugs, almost no progress has been achieved with regard to the development of novel insulin-sensitizing agents. As insulin resistance is the most eminent factor in the patho-etiology of T2D, it is not surprising that an alarming number of patients still fail to meet glycemic goals. Owing to its wealth of chemical structures, the plant kingdom is considered as an inventory of compounds exerting various bioactivities, which might be used as a basis for the development of novel medications for various pathologies. Antidiabetic activity is found in over 400 plant species, and is attributable to varying mechanisms of action. Nevertheless, relatively limited evidence exists regarding phytochemicals directly activating insulin signaling, which is the focus of this review. Here, we will list plants and phytochemicals that have been found to improve insulin sensitivity by activation of the insulin signaling cascade, and will describe the active constituents and their mechanism of action. Full article

(This article belongs to the Special Issue The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes)

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