Glucotoxicity and beta-cell failure in type 2 diabetes mellitus

J Pediatr Endocrinol Metab. 2003 Jan;16(1):5-22. doi: 10.1515/jpem.2003.16.1.5.


Type 2 diabetes mellitus is increasing worldwide with a trend of declining age of onset. It is characterized by insulin resistance and a progressive loss of beta-cell function. The ability to secrete adequate amounts of insulin is determined by the functional integrity of beta-cells and their overall mass. Glucose, the main regulator of insulin secretion and production, exerts negative effects on beta-cell function when present in excessive amounts over a prolonged period. The multiple metabolic aberrations induced by chronic hyperglycemia in the beta-cell include increased sensitivity to glucose, increased basal insulin release, reduced response to stimulus to secrete insulin, and a gradual depletion of insulin stores. Inadequate insulin production during chronic hyperglycemia results from decreased insulin gene transcription due to hyperglycemia-induced changes in the activity of beta-cell specific transcription factors. Hyperglycemia may negatively affect beta-cell mass by inducing apoptosis without a compensatory increase in beta-cell proliferation and neogenesis. The detrimental effect of excessive glucose concentrations is referred to as 'glucotoxicity'. The present review discusses the role of glucotoxicity in beta-cell dysfunction in type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Survival
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Humans
  • Hyperglycemia / etiology*
  • Insulin / biosynthesis
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / physiopathology*


  • Insulin