Epigallocatechin Gallate (EGCG) and Rutin Suppress the Glucotoxicity through Activating IRS2 and AMPK Signaling in Rat Pancreatic β Cells

• Published in: Journal of agricultural and food chemistry 2009-10, Vol.57 (20), p.9817-9827
• Main Authors: Cai, Erica P, Lin, Jen-Kun
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; animal models; Animals; biochemical pathways; Biological and medical sciences; Catechin - analogs & derivatives; Catechin - pharmacology; cell cycle; Cell Line, Tumor; cytotoxicity; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Down-Regulation; epigallocatechin; epigallocatechin gallate; Food industries; Fundamental and applied biological sciences. Psychology; gallic acid; glucose; Glucose - toxicity; Humans; in vitro studies; insulin; Insulin Receptor Substrate Proteins - genetics; Insulin Receptor Substrate Proteins - metabolism; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; islets of Langerhans; lipid metabolism; mitochondria; Molecular Nutrition; noninsulin-dependent diabetes mellitus; pancreas; Rats; rutin; Rutin - pharmacology; signal transduction; Signal Transduction - drug effects; viability
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf902618v

Pancreatic β cell failure is one critical metabolic disorder in the development of type 2 diabetes. Decreased viability and dysfunction of β cells would accelerate the diabetic pathogenesis associated with higher mortality. In this study, the tea polyphenol EGCG (epigallocatechin gallate) and the buckwheat flavonoid Rutin were investigated to attenuate the induced glucotoxicity in β cells. EGCG and Rutin could preserve the insulin secretory machinery and stimulate insulin receptor substrate 2 (IRS2) signaling in rat pancreatic β cells, RIN-m5F. These findings further demonstated the reduced glucolipotoxic effects of EGCG and Rutin through activating AMP-activated protein kinase (AMPK) signaling to inhibit the activities of lipogenic enzymes and ameliorating mitochondrial function. Consequently, the cell viability was retained after attenuating the glucotoxicity through the broad effect of EGCG and Rutin. The intrinsic protective effects of EGCG and Rutin in preserving the insulin signaling and regulating lipogenesis, manipulating cell cycling, and maintaining mitochondrial function to achieve the integrity of β cells, which highlight the possibilities of EGCG and Rutin as novel strategies for the prevention of type 2 diabetes.