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A radical explanation for glucose-induced beta cell dysfunction.

Michael Brownlee
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Abstract

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. 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.

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Adenosine DiphosphateAdenosine TriphosphateAnimalsBlood GlucoseGlucoseHumansInsulinInsulin SecretionIon ChannelsIslets of LangerhansMembrane Transport ProteinsMitochondriaMitochondrial ProteinsModels, BiologicalPancreatic DiseasesSuperoxidesUncoupling Protein 2Journal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Comment

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Michael Brownlee. 2003. A radical explanation for glucose-induced beta cell dysfunction.. https://doi.org/10.1172/jci20501

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