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

Abstract

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.

• Authors: S Bhattacharya, N Oksbjerg, J F Young, P B Jeppesen
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 16 Issue 7 Pg. 602-12 (Jul 2014) ISSN: 1463-1326 [Electronic] England
• PMID: 24205999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons Ltd.

Chemical References

• Caffeic Acids
• Flavanones
• Insulin
• Plant Preparations
• RNA, Messenger
• Quercetin
• Glucokinase
• naringenin
• Glucose
• caffeic acid

Topics

• Animals
• Biological Transport
• Caffeic Acids (pharmacology)
• Cell Line
• Cell Survival
• Flavanones (pharmacology)
• Gene Expression (drug effects)
• Glucokinase (metabolism)
• Glucose (metabolism)
• Insulin (metabolism)
• Insulin Secretion
• Insulin-Secreting Cells (drug effects, metabolism)
• Phytotherapy
• Plant Preparations (pharmacology)
• Quercetin (pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Secretory Pathway (drug effects)
• Signal Transduction (drug effects)