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Regulation of pancreatic β-cell growth and survival by the serine/threonine protein kinase Akt1/PKBα

Abstract

The physiological performance of an organ depends on an interplay between changes in cellular function and organ size, determined by cell growth, proliferation and death. Nowhere is this more evident than in the endocrine pancreas, where disturbances in function or mass result in severe disease. Recently, the insulin signal-transduction pathway has been implicated in both the regulation of hormone secretion from β cells in mammals as well as the determination of cell and organ size in Drosophila melanogaster. A prominent mediator of the actions of insulin and insulin-like growth factor 1 (IGF-1) is the 3′-phosphoinositide–dependent protein kinase Akt, also known as protein kinase B (PKB). Here we report that overexpression of active Akt1 in the mouse β cell substantially affects compartment size and function. There was a significant increase in both β-cell size and total islet mass, accompanied by improved glucose tolerance and complete resistance to experimental diabetes.

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Figure 1: Confirmation of transgene expression.
Figure 2: Expression of myr-Akt1 increases β-cell mass.
Figure 3: Myr-Akt1 expression is β-cell specific and augments cell size in an autonomous manner.
Figure 4: Metabolic effects of myr-Akt1 expression in the β cell.
Figure 5: Myr-Akt1 prevents low-dose streptozotocin-induced diabetes mellitus through suppression of apoptosis.

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Acknowledgements

The authors gratefully acknowledge services provided by the Center for Molecular Studies in Digestive and Liver Disease (Grant P30DK50306) and the Penn Diabetes Center (Grant DK19525). We thank B. Wolf, R. Ahima, and F. Matschinsky for helpful discussions and advice; and Q. Chu for technical assistance. This work was supported by grants from the National Institute of Health (R01 DK56886).

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Correspondence to Morris J. Birnbaum.

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Tuttle, R., Gill, N., Pugh, W. et al. Regulation of pancreatic β-cell growth and survival by the serine/threonine protein kinase Akt1/PKBα. Nat Med 7, 1133–1137 (2001). https://doi.org/10.1038/nm1001-1133

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