Inadequate beta-cell function is an essential component of all forms of diabetes. The most obvious problem is a failure to maintain sufficient beta-cell mass and function to cope with whatever insulin resistance is present. The most striking functional defect is a loss of acute glucose-induced insulin secretion (GIIS). This review discusses the ways in which beta-cells successfully adapt to increased demand and then decompensate as diabetes develops. Successful adaptation is achieved through increased beta-cell mass and increased insulin secretion. The hypothesis is explored that beta-cells exposed to the diabetic milieu lose their differentiation, which leads to loss of specialized functions such as GIIS. This concept has been strengthened by the finding of dedifferentiation of beta-cells in a rat model of partial pancreatectomy that includes a reduction of insulin gene expression, which may further contribute to decreased insulin production. Another finding was increased expression of c-Myc, which probably contributes to an increase in the expression of lactate dehydrogenase and the development of beta-cell hypertrophy. Arguments are developed that the beta-cell changes found in diabetes are better correlated with increased glucose levels than with non-esterified fatty acid levels, thus supporting the importance of glucose toxicity.
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February 01 2001
Beta-cell adaptation and decompensation during the progression of diabetes.
G C Weir;
G C Weir
Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA. [email protected]
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D R Laybutt;
D R Laybutt
Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA. [email protected]
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H Kaneto;
H Kaneto
Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA. [email protected]
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S Bonner-Weir;
S Bonner-Weir
Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA. [email protected]
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A Sharma
A Sharma
Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA. [email protected]
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Citation
G C Weir, D R Laybutt, H Kaneto, S Bonner-Weir, A Sharma; Beta-cell adaptation and decompensation during the progression of diabetes.. Diabetes 1 February 2001; 50 (suppl_1): S154–9. https://doi.org/10.2337/diabetes.50.2007.S154
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