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Caffeic acid, naringenin and quercetin enhance glucose‐stimulated insulin secretion and glucose sensitivity in INS‐1E cells

过剩2 葡萄糖激酶 过剩4 IRS1 葡萄糖转运蛋白 胰岛素 葡萄糖摄取 内科学 内分泌学 柚皮素 生物 胰岛素受体 生物化学 化学 胰岛素抵抗 医学 类黄酮 抗氧化剂
作者
S. Bhattacharya,N. Oksbjerg,J.F. Young,Per Bendix Jeppesen
出处
期刊:Diabetes, Obesity and Metabolism [Wiley]
卷期号:16 (7): 602-612 被引量:101
标识
DOI:10.1111/dom.12236
摘要

Aims Caffeic acid, naringenin and quercetin are naturally occurring phenolic compounds ( PCs ) present in many plants as secondary metabolites. The aim of this study was to investigate their effect on glucose‐stimulated insulin secretion ( GSIS ) in INS‐1E cells and to explore their effect on expression of genes involved in β‐cell survival and function under normoglycaemic and glucotoxic conditions. Methods For acute studies, INS‐1E cells were grown in 11 mM glucose (72 h) and then incubated with the PCs (1 h) with 3.3/16.7 mM glucose; whereas, for chronic studies, the cells were grown in 11 mM glucose (72 h) with/without the PCs , and then incubated with 3.3/16.7 mM glucose (1 h); thereafter, GSIS was measured. For GSIS and gene expression studies ( GES ) under glucotoxic conditions, two sets of cells were grown in 11/25 mM glucose with/without the PCs (72 h): one was used for GES , using real time RT‐PCR , and the other was exposed to 3.3/16.7 mM glucose, followed by measurement of GSIS . Results The study demonstrated that the PCs can enhance GSIS under hyperglycaemic and glucotoxic conditions in INS‐1E cells. Moreover, these compounds can differentially, yet distinctly change the expression profile of genes [Glut2 (glucose transporter 2), Gck (glucokinase), Ins1 (insulin 1), Ins2, Beta2 (neurogenic differentiation protein 1), Pdx1 (pancreatic and duodenal homeobox protein 1), Akt1 (RAC‐α serine/threonine‐protein kinase encoding gene), Akt2 (RAC‐β serine/threonine‐protein kinase encoding gene), Irs1 (insulin receptor substrate 1), Acc1 (acetyl CoA carboxylase 1), Bcl2 (β‐cell lymphoma 2 protein), Bax (Bcl‐2 associated X protein), Casp3 (Caspase 3), Hsp70 (heat shock protein 70), and Hsp90] involved in β‐cell stress, survival and function. Conclusion The results indicate that the PCs tested enhance GSIS and glucose sensitivity in INS‐1E cells. They also modulate gene expression profiles to improve β‐cell survival and function during glucotoxicity.
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