Glucotoxicity and β-cell failure in type 2 diabetes mellitus

Nurit Kaiser*, Gil Leibowitz, Rafael Nesher

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

185 Scopus citations

Abstract

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 β-cell function. The ability to secrete adequate amounts of insulin is determined by the functional integrity of β-cells and their overall mass. Glucose, the main regulator of insulin secretion and production, exerts negative effects on β-cell function when present in excessive amounts over a prolonged period. The multiple metabolic aberrations induced by chronic hyperglycemia in the β-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 β-cell specific transcription factors. Hyperglycemia may negatively affect β-cell mass by inducing apoptosis without a compensatory increase in β-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 β-cell dysfunction in type 2 diabetes mellitus.

Original languageAmerican English
Pages (from-to)5-22
Number of pages18
JournalJournal of Pediatric Endocrinology and Metabolism
Volume16
Issue number1
DOIs
StatePublished - 2003
Externally publishedYes

Keywords

  • Glucotoxicity
  • Hyperglycemia
  • Insulin gene transcription
  • Insulin secretion
  • Reactive oxygen species
  • β-cell
  • β-cell apoptosis
  • β-cell mass
  • β-cell proliferation

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