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Islet β cell failure in type 2 diabetes
Marc Prentki, Christopher J. Nolan
Marc Prentki, Christopher J. Nolan
Published July 3, 2006
Citation Information: J Clin Invest. 2006;116(7):1802-1812. https://doi.org/10.1172/JCI29103.
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Review Series

Islet β cell failure in type 2 diabetes

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Abstract

The major focus of this Review is on the mechanisms of islet β cell failure in the pathogenesis of obesity-associated type 2 diabetes (T2D). As this demise occurs within the context of β cell compensation for insulin resistance, consideration is also given to the mechanisms involved in the compensation process, including mechanisms for expansion of β cell mass and for enhanced β cell performance. The importance of genetic, intrauterine, and environmental factors in the determination of “susceptible” islets and overall risk for T2D is reviewed. The likely mechanisms of β cell failure are discussed within the two broad categories: those with initiation and those with progression roles.

Authors

Marc Prentki, Christopher J. Nolan

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Figure 1

Islet β cell failure and the natural history of T2D.

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Islet β cell failure and the natural history of T2D.
T2D develops in res...
T2D develops in response to overnutriton and lack of physical activity in subjects that have underlying genetic and acquired predispositions to both insulin resistance (and/or hyperinsulinemia) and β cell dysfunction. Over time, islet β cell compensation for the insulin resistance fails, resulting in a progressive decline in β cell function. As a consequence, subjects progress from normal glucose tolerance (NGT) to IGT and finally to established T2D. Even after diagnosis of T2D, β cell function continues to worsen such that subjects progress from needing changes in diet/exercise only to requiring oral hypoglycemic agents and eventually insulin for achievement of adequate glycemic control. Future therapies will be directed not only to achievement of euglycemia, but also changing the course of the disease by reversing the processes of β cell failure.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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