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- Title
Genetic and biochemical pathways of β-cell failure in type 2 diabetes.
- Authors
Talchai, C.; Lin, H. V.; Kitamura, T.; Accili, D.
- Abstract
We review mechanisms of β-cell failure in type 2 diabetes. A wealth of information indicates that it is caused by impaired insulin secretion and decreased β-cell mass. Interestingly, there appears to be a link between these two mechanisms. The earliest reaction to peripheral insulin resistance is an increase in insulin production, owing primarily to increased secretion, and to a lesser extent to decreased clearance. Experimental animal models indicate that hyperinsulinaemia promotes an increase in β-cell mass, largely via increased β-cell replication. In contrast, following the onset of overt diabetes, there is a slowly progressive loss of β-cell function and mass, both in animal models and in diabetic humans. It is of great interest that most diabetes-associated genes identified in genome-wide association studies appear to be enriched in the β-cell and to have the potential to regulate mass and/or function. Here, we review evidence derived from experimental animal models to unravel the mechanisms underlying β-cell dysfunction. We focus primarily on signalling pathways, as opposed to nutrient sensing, and specifically on the notion that insulin and growth factor signalling via Foxo1 in pancreatic β-cells links insulin secretion with cellular proliferation and survival.
- Subjects
DIABETES complications; CELL death; INSULIN; INSULIN resistance; CELL proliferation; DISEASE risk factors
- Publication
Diabetes, Obesity & Metabolism, 2009, Vol 11, p38
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/j.1463-1326.2009.01115.x