Genistein Acutely Stimulates Insulin Secretion in Pancreatic -Cells Through a cAMP-Dependent Protein Kinase Pathway

Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
Diabetes (Impact Factor: 8.1). 05/2006; 55(4):1043-50. DOI: 10.2337/diabetes.55.04.06.db05-1089
Source: PubMed


Although genistein, a soy isoflavone, has beneficial effects on various tissues, it is unclear whether it plays a role in physiological insulin secretion. Here, we present evidence that genistein increases rapid glucose-stimulated insulin secretion (GSIS) in both insulin-secreting cell lines (INS-1 and MIN6) and mouse pancreatic islets. Genistein elicited a significant effect at a concentration as low as 10 nmol/l with a maximal effect at 5 micromol/l. The effect of genistein on GSIS was not dependent on estrogen receptor and also not related to an inhibition of protein tyrosine kinase (PTK). Consistent with its effect on GSIS, genistein increases intracellular cAMP and activates protein kinase A (PKA) in both cell lines and the islets by a mechanism that does not involve estrogen receptor or PTK. The induced cAMP by genistein, at physiological concentrations, may result primarily from enhanced adenylate cyclase activity. Pharmacological or molecular intervention of PKA activation indicated that the insulinotropic effect of genistein is primarily mediated through PKA. These findings demonstrated that genistein directly acts on pancreatic beta-cells, leading to activation of the cAMP/PKA signaling cascade to exert an insulinotropic effect, thereby providing a novel role of soy isoflavones in the regulation of insulin secretion.

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    • "The results of mRNA and western blotting showed that 7WA-induced enhancement of GSIS is mediated, at least partially, by the cAMP-PKA dependent pathway. Therefore, to examine which pathway(s) is involved in 7WA-induced enhancement of GSIS, RIN-5F cells were pretreated with 10 ␮mol/L SQ22536 (an AC inhibitor) (Liu et al., 2006 "
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    ABSTRACT: A water-soluble polysaccharide, 7WA, with an average molecular mass of 7.1×10(4)Da, was isolated from the leaves of green tea. Monosaccharide composition analysis indicated that 7WA mainly contained Arabinose and Galactose in the molar ratio of 1.0:0.96. By using the methods of methylation analysis, partial hydrolysis, and NMR, 7WA was characterized to possess a backbone consisting of 1,3- and 1,6-linked galactopyranosyl residues, with branches attached to O-3 of 1,6-linked galactose residues, and O-4 and O-6 of 1,3-linked galactose residues. The results of glucose-stimulated insulin secretion (GSIS) showed that 7WA significantly augmented insulin secretion at high glucose level (25mM), however, such effect was not seen at low glucose level (5mM). The mechanism study results indicated 7WA, a type II arabinogalactan from Green Tea, enhances GSIS through cAMP-PKA pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Carbohydrate Polymers 06/2015; 124:98-108. DOI:10.1016/j.carbpol.2015.01.070 · 4.07 Impact Factor
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    • "Likewise, polyphenols have the potential to trigger phosphatidylinositide 3-kinase (PI3K), an intracellular signal transducer for the upregulation of blood glucose uptake (Kumar et al., 2009). The antihyperglycemic effect of genistein did not correlate with induction of insulin biosynthesis, glucose transporter-2 expression, or glycolytic pathway, rather than it acts as a novel agonist in cAMP-dependent protein kinase signaling, which is an important physiological inducer of pancreatic b-cells for glucose-induced insulin secretion (Liu et al., 2006). Genistein, an isoflavone, demonstrated antidiabetic effect by positively harmonizing the pancreatic b-cell functions through activation of cyclic AMP/PKA-dependent ERK1/2 signaling pathway (Fu et al., 2010). "
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    ABSTRACT: Context: Polyphenol-rich marine macroalgae are gaining dietary importance due to their influence over diabetes mellitus and the role as a vital source of high-value nutraceuticals. Their assorted beneficial effects on human health include competitive inhibition of digestive enzymes, varying the activity of hepatic glucose-metabolizing enzymes, lowering the plasma glucose levels, and lipid peroxidation, delaying the aging process. Objective: In this paper, we review the health beneficial effects of polyphenols and phlorotannins from brown seaweeds with special emphasis on their inhibitory effects on carbohydrate-metabolizing enzymes. Methods: A survey of literature from databases such as Sciencedirect, Scopus, Pubmed, Springerlink, and Google Scholar from the year 1973 to 2013 was done to bring together the information relating to drug discovery from brown seaweeds as a source for diabetes treatment. Results: Over the past two decades, 20 different bioactive polyphenols/phlorotannins have been isolated and studied from 10 different brown algae. Discussion of the positive effect on the inhibition of enzymes metabolizing carbohydrates in both in vitro and in vivo experiments are included. Conclusion: Despite the recent advancements in isolating bioactive compounds from seaweeds with potential health benefit or pharmaceutical behavior, studies on the polyphenol effectiveness on glucose homeostasis in human beings are very few in response to their functional characterization. Added research in this area is required to confirm the close connection of polyphenol rich seaweed-based diet consumption with glucose homeostasis and the exciting possibility of prescribing polyphenols to treat the diabetes pandemic.
    Pharmaceutical Biology 01/2015; 53(8). DOI:10.3109/13880209.2014.959615 · 1.24 Impact Factor
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    • "Insulin secreted in supernatants was measured by an ELISA kit. Human islets (100 islets/tube) were incubated in 3 or 20 mM glucose with or without various concentrations of baicalein in a 37°C water bath with gentle shaking for 30 min [28]. Insulin in the supernatants was measured by ELISA and normalized to protein content in the same sample. "
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    ABSTRACT: In both type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and progressive dysfunction of β-cell, leading to the impaired insulin secretion. Here, we show that dietary supplementation of baicalein, a flavone isolated from the roots of Chinese herb Scutellaria baicalensis, improved glucose tolerance and enhanced glucose-stimulated insulin secretion (GSIS) in high-fat diet (HFD-) induced middle-aged obese mice. Baicalein had no effect on food intake, body weight gain, circulating lipid profile, and insulin sensitivity in obese mice. Using another mouse model of type 2 diabetes generated by high-fat diet (HFD) feeding and low doses of streptozotocin injection, we found that baicalein treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in these middle-aged obese diabetic mice, which are associated with the improved islet β-cell survival and mass. In the in vitro studies, baicalein significantly augmented GSIS and promoted viability of insulin-secreting cells and human islets cultured either in the basal medium or under chronic hyperlipidemic condition. These results demonstrate that baicalein may be a naturally occurring antidiabetic agent by directly modulating pancreatic β-cell function.
    International Journal of Endocrinology 07/2014; 2014:846742. DOI:10.1155/2014/846742 · 1.95 Impact Factor
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