Cyclin D2 is Essential for the Compensatory Beta-Cell Hyperplastic Response to Insulin Resistance in Rodents

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Cyclin D2 is Essential for the Compensatory Beta-Cell Hyperplastic Response to Insulin Resistance in Rodents

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Title: Cyclin D2 is Essential for the Compensatory Beta-Cell Hyperplastic Response to Insulin Resistance in Rodents
Author: Georgia, Senta; Hinault, Charlotte; Kawamori, Dan; Hu, Jiang; Kanji, Murtaza; Bhushan, Anil; Meyer, John; Kulkarni, Rohit Narayan

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Citation: Georgia, Senta, Charlotte Hinault, Dan Kawamori, Jiang Hu, John Meyer, Murtaza Kanji, Anil Bhushan, and Rohit N. Kulkarni. 2010. Cyclin D2 is essential for the compensatory beta-cell hyperplastic response to insulin resistance in rodents. Diabetes 59(4): 987-996.
Access Status: At the direction of the depositing author this work is not currently accessible through DASH.
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Abstract: OBJECTIVE: A major determinant of the progression from insulin resistance to the development of overt type 2 diabetes is a failure to mount an appropriate compensatory β-cell hyperplastic response to maintain normoglycemia. We undertook the present study to directly explore the significance of the cell cycle protein cyclin D2 in the expansion of β-cell mass in two different models of insulin resistance. RESEARCH DESIGN AND METHODS: We created compound knockouts by crossing mice deficient in cyclin D2 (D2KO) with either the insulin receptor substrate 1 knockout (IRS1KO) mice or the insulin receptor liver-specific knockout mice (LIRKO), neither of which develops overt diabetes on its own because of robust compensatory β-cell hyperplasia. We phenotyped the double knockouts and used RT-qPCR and immunohistochemistry to examine β-cell mass. RESULTS: Both compound knockouts, D2KO/LIRKO and D2KO/IRS1KO, exhibited insulin resistance and hyperinsulinemia and an absence of compensatory β-cell hyperplasia. However, the diabetic D2KO/LIRKO group rapidly succumbed early compared with a relatively normal lifespan in the glucose-intolerant D2KO/IRS1KO mice. CONCLUSIONS: This study provides direct genetic evidence that cyclin D2 is essential for the expansion of β-cell mass in response to a spectrum of insulin resistance and points to the cell-cycle protein as a potential therapeutic target that can be harnessed for preventing and curing type 2 diabetes.
Published Version: doi:10.2337/db09-0838
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844846/pdf/
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:8296046

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