TY - JOUR
T1 - Growth hormone receptor regulates β cell hyperplasia and glucose-stimulated insulin secretion in obese mice
AU - Wu, Yingjie
AU - Liu, Chengyu
AU - Sun, Hui
AU - Vijayakumar, Archana
AU - Giglou, Pejman Raeisi
AU - Qiao, Ruifang
AU - Oppenheimer, Joshua
AU - Yakar, Shoshana
AU - LeRoith, Derek
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Insulin, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) play key roles in the regulation of β cell growth and function. Although β cells express the GH receptor, the direct effects of GH on β cells remain largely unknown. Here we have employed a rat insulin II promoter-driven (RIP-driven) Cre recombinase to disrupt the GH receptor in β cells (βGHRKO). βGHRKO mice fed a standard chow diet exhibited impaired glucose-stimulated insulin secretion but had no changes in β cell mass. When challenged with a high-fat diet, βGHRKO mice showed evidence of a β cell secretory defect, with further deterioration of glucose homeostasis indicated by their altered glucose tolerance and blunted glucose-stimulated insulin secretion. Interestingly, βGHRKO mice were impaired in β cell hyperplasia in response to a high-fat diet, with decreased β cell proliferation and overall reduced β cell mass. Therefore, GH receptor plays critical roles in glucose-stimulated insulin secretion and β cell compensation in response to a high-fat diet.
AB - Insulin, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) play key roles in the regulation of β cell growth and function. Although β cells express the GH receptor, the direct effects of GH on β cells remain largely unknown. Here we have employed a rat insulin II promoter-driven (RIP-driven) Cre recombinase to disrupt the GH receptor in β cells (βGHRKO). βGHRKO mice fed a standard chow diet exhibited impaired glucose-stimulated insulin secretion but had no changes in β cell mass. When challenged with a high-fat diet, βGHRKO mice showed evidence of a β cell secretory defect, with further deterioration of glucose homeostasis indicated by their altered glucose tolerance and blunted glucose-stimulated insulin secretion. Interestingly, βGHRKO mice were impaired in β cell hyperplasia in response to a high-fat diet, with decreased β cell proliferation and overall reduced β cell mass. Therefore, GH receptor plays critical roles in glucose-stimulated insulin secretion and β cell compensation in response to a high-fat diet.
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U2 - 10.1172/JCI45027
DO - 10.1172/JCI45027
M3 - Article
C2 - 21555853
AN - SCOPUS:79957887666
SN - 0021-9738
VL - 121
SP - 2422
EP - 2426
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 6
ER -