Cyclin D2 is Essential for the Compensatory Beta-Cell Hyperplastic Response to Insulin Resistance in Rodents
Access StatusFull text of the requested work is not available in DASH at this time ("dark deposit"). For more information on dark deposits, see our FAQ.
MetadataShow full item record
CitationGeorgia, 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.
AbstractOBJECTIVE: 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8296046
- HMS Scholarly Articles