Failure of beta-cell adaptation in type 2 diabetes: Lessons from animal models

Front Biosci (Landmark Ed). 2009 Jan 1;14:1099-115. doi: 10.2741/3296.


The pancreatic beta-cell adapts to increased nutrient availability and insulin resistance by increasing its function and mass. These processes are orchestrated by signals derived from nutrient metabolism, hormones and cytokines. Their end-result is the regulation of insulin secretion and biosynthesis, and beta-cell proliferation and apoptosis. This review focuses on the mechanisms involved in beta-cell nutrient sensing and adaptation and the potential causes of beta-cell dysfunction and death in type 2 diabetes mellitus. Understanding the mechanisms that regulate adequate beta-cell adaptation and the natural history of beta-cell failure is of utmost importance for the development of novel disease modifying treatments.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / pathology*
  • Disease Models, Animal*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology*
  • Proinsulin / biosynthesis
  • Proinsulin / metabolism


  • Proinsulin