title: Growth hormone receptor regulates β cell hyperplasia and glucose-stimulated insulin secretion in obese mice.
abstract: 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.
authors.affiliation: Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wu
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Archana
authors.initials: A
authors.lastname: Vijayakumar
authors.forename: Pejman Raeisi
authors.initials: PR
authors.lastname: Giglou
authors.forename: Ruifang
authors.initials: R
authors.lastname: Qiao
authors.forename: Joshua
authors.initials: J
authors.lastname: Oppenheimer
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
mesh_terms: D000821:Animal Feed; D000818:Animals; D002455:Cell Division; D004041:Dietary Fats / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000502:physiology*; D018149:Glucose Intolerance / Q000209:etiology* / Q000503:physiopathology; D006965:Hyperplasia; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D009928:Organ Specificity; D051381:Rats; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D050799:STAT5 Transcription Factor / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D007328:Insulin; D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; D005947:Glucose