Resveratrol Potentiates Glucose-stimulated Insulin Secretion in INS-1E β-Cells and Human Islets through a SIRT1-dependent Mechanism

Vetterli, Laurène; Brun, Thierry; Giovannoni, Laurianne; Bosco, Domenico; Maechler, Pierre

doi:10.1074/jbc.m110.176842

Cited by 153 publications

(148 citation statements)

References 67 publications

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“…Islets were isolated by collagenase digestion (collagenase P, Roche) as detailed elsewhere (Carobbio et al, 2004) and cultured overnight free floating in RPMI-1640 medium (Gibco) supplemented with 10% (v/v) heatinactivated fetal calf serum (FCS), 2 mM glutamine, 10 mM Hepes, 100 U/ml penicillin, 100 g/ml streptomycin, 1 mM sodium pyruvate and 50 M 2-mercaptoethanol. Human islets were isolated from pancreases of deceased multiorgan donors, who had provided written informed consent (ECIT consortium), and maintained in CMRL-1066 before experiments (Vetterli et al, 2011). Rat insulinoma INS-1E ß-cells were cultured in RPMI-1640 as detailed previously (Merglen et al, 2004).…”

Section: Pancreatic Islet and Cell Preparationsmentioning

confidence: 99%

Epigallocatechin-3-gallate (EGCG) activates AMPK through the inhibition of glutamate dehydrogenase in muscle and pancreatic ß-cells: A potential beneficial effect in the pre-diabetic state?

Pournourmohammadi

Grimaldi

Stridh

et al. 2017

The International Journal of Biochemistry & Cell Biology

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a b s t r a c tGlucose homeostasis is determined by insulin secretion from the ß-cells in pancreatic islets and by glucose uptake in skeletal muscle and other insulin target tissues. While glutamate dehydrogenase (GDH) senses mitochondrial energy supply and regulates insulin secretion, its role in the muscle has not been elucidated. Here we investigated the possible interplay between GDH and the cytosolic energy sensing enzyme 5 -AMP kinase (AMPK), in both isolated islets and myotubes from mice and humans. The green tea polyphenol epigallocatechin-3-gallate (EGCG) was used to inhibit GDH. Insulin secretion was reduced by EGCG upon glucose stimulation and blocked in response to glutamine combined with the allosteric GDH activator BCH (2-aminobicyclo-[2,2,1] heptane-2-carboxylic acid). Insulin secretion was similarly decreased in islets of mice with ß-cell-targeted deletion of GDH (ßGlud1 −/− ). EGCG did not further reduce insulin secretion in the mutant islets, validating its specificity. In human islets, EGCG attenuated both basal and nutrient-stimulated insulin secretion. Glutamine/BCH-induced lowering of AMPK phosphorylation did not operate in ßGlud1 −/− islets and was similarly prevented by EGCG in control islets, while high glucose systematically inactivated AMPK. In mouse C2C12 myotubes, like in islets, the inhibition of AMPK following GDH activation with glutamine/BCH was reversed by EGCG. Stimulation of GDH in primary human myotubes caused lowering of insulin-induced 2-deoxy-glucose uptake, partially counteracted by EGCG. Thus, mitochondrial energy provision through anaplerotic input via GDH influences the activity of the cytosolic energy sensor AMPK. EGCG may be useful in obesity by resensitizing insulin-resistant muscle while blunting hypersecretion of insulin in hypermetabolic states.

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Section: Pancreatic Islet and Cell Preparationsmentioning

confidence: 99%

Epigallocatechin-3-gallate (EGCG) activates AMPK through the inhibition of glutamate dehydrogenase in muscle and pancreatic ß-cells: A potential beneficial effect in the pre-diabetic state?

Pournourmohammadi

Grimaldi

Stridh

et al. 2017

The International Journal of Biochemistry & Cell Biology

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“…Besides, recent evidence demonstrated that the improvement of GSIS in INS-1 cells and human islets by the Sirt1 activator resveratrol was dependent on active Sirt1 (Vetterli et al, 2011). Furthermore, it was found that Sirt1 could promote insulin secretion in pancreatic beta cells in response to glucose, partly, through the repression of UCP2 (Moynihan et al, 2005;Bordone et al, 2006;Ramsey et al, 2008) (Fig.…”

Section: Silent Information Regulator 2 Proteinmentioning

confidence: 99%

Signaling Molecules Involved in Lipid-Induced Pancreatic Beta-Cell Dysfunction

Shao

Yang

Yuan

et al. 2013

DNA and Cell Biology

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The increasing incidence of type 2 diabetes mellitus is partially due to the rising obesity rates and the elevated levels of free fatty acids (FFAs). It is known that FFAs are putative mediators of beta-cell dysfunction, which is characterized with impaired glucose-stimulated insulin secretion and increased apoptosis, being defined as lipotoxicity. To date, many factors and their related signal pathways have been reported to be involved in FFAinduced beta-cell dysfunction. However, the entire blueprint is still not obtained. Some essential and newfound effectors, including the sterol regulatory element-binding protein (SREBP)-1c, farnesoid X receptor (FXR), forkhead box-containing protein O (FoxO) 1, ubiquitin C-terminal hydrolase L (UCHL) 1, N-myc downstreamregulated gene (NDRG) 2, perilipin family proteins, silent information regulator 2 protein 1 (Sirt1), pituitary adenylate cyclase-activating polypeptide (PACAP), and ghrelin are described in this review, which may help to further understand the molecular network for lipotoxicity.

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“…95 The dietary polyphenol resveratrol (one of the first activators of SIRT1 to be identified) exerts an anti-diabetic activity by regulating the activity of AMPK and PGC1a. 96,97 Due to the scientific evidence about the biologic activities of resveratrol, its efficacy for the treatment of several aging-related pathologies including T2DM has been clinically evaluated. 98 Moreover, synthetic SIRT1 activators, such as SRT1720, have been developed to improve glucose homeostasis and insulin sensitivity in animal models of T2DM.…”

Section: Nct02046395mentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling b-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on b-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

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Resveratrol Potentiates Glucose-stimulated Insulin Secretion in INS-1E β-Cells and Human Islets through a SIRT1-dependent Mechanism

Cited by 153 publications

References 67 publications

Epigallocatechin-3-gallate (EGCG) activates AMPK through the inhibition of glutamate dehydrogenase in muscle and pancreatic ß-cells: A potential beneficial effect in the pre-diabetic state?

Epigallocatechin-3-gallate (EGCG) activates AMPK through the inhibition of glutamate dehydrogenase in muscle and pancreatic ß-cells: A potential beneficial effect in the pre-diabetic state?

Signaling Molecules Involved in Lipid-Induced Pancreatic Beta-Cell Dysfunction

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

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