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pubmed:abstractText |
Insulin, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) play key roles in the regulation of ? cell growth and function. Although ? cells express the GH receptor, the direct effects of GH on ? cells remain largely unknown. Here we have employed a rat insulin II promoter-driven (RIP-driven) Cre recombinase to disrupt the GH receptor in ? cells (?GHRKO). ?GHRKO mice fed a standard chow diet exhibited impaired glucose-stimulated insulin secretion but had no changes in ? cell mass. When challenged with a high-fat diet, ?GHRKO mice showed evidence of a ? cell secretory defect, with further deterioration of glucose homeostasis indicated by their altered glucose tolerance and blunted glucose-stimulated insulin secretion. Interestingly, ?GHRKO mice were impaired in ? cell hyperplasia in response to a high-fat diet, with decreased ? cell proliferation and overall reduced ? cell mass. Therefore, GH receptor plays critical roles in glucose-stimulated insulin secretion and ? cell compensation in response to a high-fat diet.
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pubmed:affiliation |
Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
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