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: Yingjie Wu, Chengyu Liu, Hui Sun, Archana Vijayakumar, Pejman Raeisi Giglou, Ruifang Qiao, Joshua Oppenheimer, Shoshana Yakar, Derek LeRoith
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 121 Issue 6 Pg. 2422-6 (Jun 2011) ISSN: 1558-8238 [Electronic] United States
• PMID: 21555853 (Publication Type: Journal Article)

Chemical References

• Dietary Fats
• Insulin
• Receptors, Somatotropin
• STAT5 Transcription Factor
• Glucose

Topics

• Animal Feed
• Animals
• Cell Division
• Dietary Fats (pharmacology, toxicity)
• Female
• Gene Knockdown Techniques
• Glucose (physiology)
• Glucose Intolerance (etiology, physiopathology)
• Hyperplasia
• Insulin (metabolism)
• Insulin Secretion
• Islets of Langerhans (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Obesity (etiology, physiopathology)
• Organ Specificity
• Rats
• Receptors, Somatotropin (antagonists & inhibitors, genetics, physiology)
• STAT5 Transcription Factor (metabolism)