Exenatide inhibits beta-cell apoptosis by decreasing thioredoxin-interacting protein

Biochem Biophys Res Commun. 2006 Aug 4;346(3):1067-74. doi: 10.1016/j.bbrc.2006.06.027. Epub 2006 Jun 13.


Exenatide (Ex-4) is a novel anti-diabetic drug that stimulates insulin secretion and enhances beta-cell mass, but the mechanisms involved are not fully understood. We found that Ex-4 protects INS-1 beta-cells against oxidative stress-induced apoptosis (TUNEL) and also reduces expression (mRNA and protein) of thioredoxin-interacting protein (TXNIP), a pro-apoptotic factor involved in beta-cell glucose toxicity and oxidative stress. This reduction was observed in INS-1 cells, mouse, and human islets as well as in wild-type mice receiving Ex-4 and was accompanied by decreased expression of the apoptotic factors caspase-3 and Bax. To determine whether Ex-4-mediated TXNIP reduction is critical for this inhibition of apoptosis, we stably overexpressed TXNIP in INS-1 cells, which completely blunted the anti-apoptotic Ex-4 effects. Thus, Ex-4 inhibits apoptosis by reducing TXNIP expression and early initiation of Ex-4 treatment may help preserve endogenous beta-cell mass, protect against oxidative stress, and delay type 2 diabetes progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Cells, Cultured
  • Exenatide
  • Gene Expression Regulation
  • Humans
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism*
  • Male
  • Mice
  • Oxidative Stress
  • Peptides / administration & dosage
  • Peptides / pharmacology*
  • Protein Binding
  • Rats
  • Thioredoxins / metabolism*
  • Venoms / administration & dosage
  • Venoms / pharmacology*


  • Carrier Proteins
  • Cell Cycle Proteins
  • Peptides
  • TXNIP protein, human
  • TXNIP protein, rat
  • Txnip protein, mouse
  • Venoms
  • Thioredoxins
  • Exenatide