Drak2 Overexpression Results in Increased Beta-Cell Apoptosis After Free Fatty Acid Stimulation

J Cell Biochem. 2008 Nov 1;105(4):1073-80. doi: 10.1002/jcb.21910.

Abstract

Drak2 is a serine threonine kinase in the death-associated protein family. In this study, we investigated its role in free fatty acid (FFA)-induced islet apoptosis. Drak2 mRNA and protein were rapidly induced in islet beta-cells after FFA stimulation. Such Drak2 upregulation was accompanied by increased beta-cell apoptosis, which was inhibited by Drak2 knockdown using siRNA. Conversely, transgenic (Tg) Drak2 overexpression led to aggravated beta-cell apoptosis triggered by FFA. Drak2 overexpression in islets compromised the increase of anti-apoptotic factors, such as Bcl-2, Bcl-xL and Flip, upon FFA assault. Further in vivo experiments demonstrated that Drak2 Tg mice presented compromised glucose tolerance in a diet-induced obesity model. Our data show that Drak2 is detrimental to islet survival in the presence of excessive lipid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / analysis
  • Diet
  • Fatty Acids, Nonesterified / pharmacology*
  • Glucose Tolerance Test
  • Insulin-Secreting Cells / cytology*
  • Mice
  • Obesity
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / pharmacology
  • RNA, Messenger
  • Up-Regulation / drug effects

Substances

  • Apoptosis Regulatory Proteins
  • Fatty Acids, Nonesterified
  • RNA, Messenger
  • Drak2 protein, mouse
  • Protein-Serine-Threonine Kinases