RESUMEN
Insulin, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) play key roles in the regulation of ß cell growth and function. Although ß cells express the GH receptor, the direct effects of GH on ß cells remain largely unknown. Here we have employed a rat insulin II promoter-driven (RIP-driven) Cre recombinase to disrupt the GH receptor in ß cells (ßGHRKO). ßGHRKO mice fed a standard chow diet exhibited impaired glucose-stimulated insulin secretion but had no changes in ß cell mass. When challenged with a high-fat diet, ßGHRKO mice showed evidence of a ß cell secretory defect, with further deterioration of glucose homeostasis indicated by their altered glucose tolerance and blunted glucose-stimulated insulin secretion. Interestingly, ßGHRKO mice were impaired in ß cell hyperplasia in response to a high-fat diet, with decreased ß cell proliferation and overall reduced ß cell mass. Therefore, GH receptor plays critical roles in glucose-stimulated insulin secretion and ß cell compensation in response to a high-fat diet.