Flavonol Kaempferol Improves Chronic Hyperglycemia-Impaired Pancreatic Beta-Cell Viability and Insulin Secretory Function

Eur J Pharmacol. 2011 Nov 16;670(1):325-32. doi: 10.1016/j.ejphar.2011.08.011. Epub 2011 Sep 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology*
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Kaempferols / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects

Substances

  • 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