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J Pediatr Endocrinol Metab. 2003 Jan;16(1):5-22.

Glucotoxicity and beta-cell failure in type 2 diabetes mellitus.

Author information

1
Endocrinology and Metabolism Service, Department of Medicine and The Hadassah Diabetes Center, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. kaiser@md.huji.ac.il

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 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.

PMID:
12585335
DOI:
10.1515/jpem.2003.16.1.5
[Indexed for MEDLINE]

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