Flavonol kaempferol improves chronic hyperglycemia-impaired pancreatic beta-cell viability and insulin secretory function.

Abstract

Considerable evidence shows that chronic hyperglycemia can cause pancreatic beta-cell dysfunction, which contributes to progressive deterioration of glucose homeostasis and overt diabetes. In the present study, we found that kaempferol, a flavonol compound present in various Chinese medicinal herbs, has cytoprotective effects on cultured clonal beta-cells and pancreatic human islets. Kaempferol treatment dose-dependently promoted viability, inhibited cellular apoptosis, and reduced caspase-3 activity in beta-cells and human islets exposed to chronic high glucose, with 10 μM kaempferol exerting the maximum effect. In addition, kaempferol treatment improved the expression of anti-apoptotic proteins Akt and Bcl-2 that was significantly reduced in beta-cells and human islets chronically exposed to hyperglycemia. Furthermore, exposure of beta-cells and human islets to kaempferol restored high glucose-attenuated intracellular cAMP and ATP production. Inhibition of protein kinase A or Akt activation ablated the anti-apoptotic effect of kaempferol. These cytoprotective effects of kaempferol were associated with improved insulin secretory function and synthesis in beta-cells and human islets. These findings provide evidence that kaempferol may be a naturally occurring anti-diabetic compound by protecting pancreatic beta-cell survival and function in a hostile environment that would otherwise lead to type 2 diabetes.

• Authors: Yanling Zhang, Dongmin Liu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 670 Issue 1 Pg. 325-32 (Nov 16 2011) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 21914439 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Insulin
• Kaempferols
• Proto-Oncogene Proteins c-bcl-2
• kaempferol
• Cyclic AMP
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Cyclic AMP-Dependent Protein Kinases
• Caspase 3

Topics

• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Survival (drug effects)
• Chronic Disease
• Cyclic AMP (biosynthesis)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Hyperglycemia (pathology)
• Insulin (biosynthesis, metabolism)
• Insulin Secretion
• Insulin-Secreting Cells (drug effects, metabolism, pathology)
• Intracellular Space (drug effects, metabolism)
• Kaempferols (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Signal Transduction (drug effects)