Diabete de type 2 et apoptose des cellules β

Translated title of the contribution: Type 2 diabetes mellitus and β cell apoptosis

E. Cerasi*, N. Kaiser, G. Leibowitz

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    24 Scopus citations

    Abstract

    Type 2 diabetes mellitus and β cell apoptosis. Type 2 diabetes mellitus features an asymptomatic insulin resistance phase preceding the onset of diabetes. Hyperglycemia occurs when a relative insulin deficiency appears, meaning that β cell secretory dysfunction is a key element in type 2 diabetes pathophysiology. So far, insulin secretion deficiency is explained by pancreatic β cell 'exhaustion' phenomena. Recent data suggest that apoptotic mechanisms could explain insulin deficiency through a reduction in the absolute pancreatic β cell number. Psammomys obesus(sand rat) is an animal model for type 2 diabetes mellitus, initially characterized by hyperinsulinism followed by insulin deficiency linked with a reduction in the number of pancreatic β cells. Transition to diabetes can be observed following changes in usual lifestyle of the sand rat. In the desert, caloric intake is low and physical expenditure is heavy. In the laboratory, animals turn diabetic as early as 4 days following a high calory diet. At a later stage, diabetes is irreversible and animals die from diabetic ketoacidosis, β cell apoptosis rate is low in non diabetic animals and increases 14-fold by 20 days after diabetes onset. At this stage, cells undergoing apoptosis can be observed, coexisting with necrotic cells without any insulitis. Similar results were obtained in vitro in isolated pancreatic islets that were exposed to increasing glucose concentrations, suggesting that chronic hyperglycemia plays a role in the onset or the deterioration of the process. However, precise mechanisms of apoptosis in this case remain poorly understood. Aminoguanidin does not prevent β cell apoptosis in vitro, suggesting that advanced glycation products or NO production are not involved in this β cell destruction process. Similar mechanisms secondary to hyperglycemia could play a role in the diabetes process in man and explain the marked insulin secretory deficiency that is sometimes observed in these patients. In addition to its preventing role on diabetes complication, the obtention of normoglycemia could help maintaining β cell function.

    Translated title of the contributionType 2 diabetes mellitus and β cell apoptosis
    Original languageFrench
    Pages (from-to)13-16
    Number of pages4
    JournalDiabetes and Metabolism
    Volume26
    Issue numberSUPPL. 3
    StatePublished - 2000

    Keywords

    • Apoptosis pancreatic β cells
    • Diabetes
    • Psammomys obesus

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