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A radical explanation for glucose-induced [beta] cell dysfunction. Brownlee, Michael [Editorial] Journal of Clinical Investigation. 112(12):1788-1790, December 2003.
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The development of type 2 diabetes requires impaired [beta] cell function. Hyperglycemia itself causes further decreases in glucose-stimulated insulin secretion. A new study demonstrates that hyperglycemia-induced mitochondrial superoxide production activates uncoupling protein 2, which decreases the ATP/ADP ratio and thus reduces the insulin-secretory response (see the related article beginning on page 1831). These data suggest that pharmacologic inhibition of mitochondrial superoxide overproduction in [beta] cells exposed to hyperglycemia could prevent a positive feed-forward loop of glucotoxicity that drives impaired glucose tolerance toward frank type 2 diabetes.
Copyright (C) 2003 The American Society for Clinical Investigation, Inc.