Pancreatic beta-cell growth and survival--a role in obesity-linked type 2 diabetes?

Trends Mol Med. 2002 Aug;8(8):375-84. doi: 10.1016/s1471-4914(02)02377-8.

Abstract

Obesity-linked type 2 diabetes is a disease of insulin resistance combined with pancreatic beta-cell dysfunction. Although a role for beta-cell mass in the pathogenesis of obesity-linked type 2 diabetes has recently gained prominence, the idea is still being developed. It is proposed that in early obesity an increase in beta-cell mass and function might compensate for peripheral insulin resistance. However, as time and/or the severity of the obesity continue, there is decay in such adaptation and the beta-cell mass becomes inadequate. This, together with beta-cell dysfunction, leads to the onset of type 2 diabetes. It is becoming evident that elements in insulin and insulin growth factor (IGF)-1 signal-transduction pathways are key to regulating beta-cell growth. Current evidence indicates that interference of insulin signaling in obesity contributes to peripheral insulin resistance. This article examines whether a similar interference of IGF-1 signaling in the beta-cell could hinder upregulation of beta-cell mass and/or function, resulting in a failure to compensate for insulin resistance.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Survival / physiology*
  • Diabetes Mellitus / physiopathology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Growth Hormone / metabolism
  • Humans
  • Hyperglycemia / metabolism
  • Hyperlipidemias / metabolism
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance / physiology
  • Insulin-Like Growth Factor I / metabolism
  • Islets of Langerhans / cytology
  • Islets of Langerhans / growth & development*
  • Islets of Langerhans / physiology
  • Mice
  • Mice, Knockout
  • Obesity*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Signal Transduction / physiology

Substances

  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Phosphoproteins
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Receptor, IGF Type 1
  • Receptor, Insulin