Cell GHS-R Regulates Insulin Secretion and Sensitivity. Academic Article uri icon


  • Growth hormone secretagogue receptor (GHS-R) is widely known to regulate food intake and adiposity, but its role in glucose homeostasis is unclear. In this study, we investigated the expression of GHS-R in mouse pancreatic islets and its role in glycemic regulation. We used Ghsr-IRES-tauGFP mice, with Green Fluorescent Protein (GFP) as a surrogate for GHS-R, to demonstrate the GFP co-localization with insulin and glucagon expression in pancreatic islets, confirming GHS-R expression in and cells. We then generated -cell-specific GHSR-deleted mice with MIP-Cre/ERT and validated that GHS-R suppression was restricted to the pancreatic islets. MIP-Cre/ERT;Ghsrf/f mice showed normal energy homeostasis with similar body weight, body composition, and indirect calorimetry profile. Interestingly, MIP-Cre/ERT;Ghsrf/f mice exhibited an impressive phenotype in glucose homeostasis. Compared to controls, MIP-Cre/ERT;Ghsrf/f mice showed lower fasting blood glucose and insulin; reduced first-phase insulin secretion during a glucose tolerance test (GTT) and glucose-stimulated insulin secretion (GSIS) test in vivo. The isolated pancreatic islets of MIP-Cre/ERT;Ghsrf/f mice also showed reduced insulin secretion during GSIS ex vivo. Further, MIP-Cre/ERT;Ghsrf/f mice exhibited improved insulin sensitivity during insulin tolerance tests (ITT). Overall, our results confirmed GHS-R expression in pancreatic and cells; GHS-R cell-autonomously regulated GSIS and modulated systemic insulin sensitivity. In conclusion, cell GHS-R was an important regulator of glucose homeostasis, and GHS-R antagonists may have therapeutic potential for Type 2 Diabetes.

published proceedings

  • Int J Mol Sci

altmetric score

  • 2

author list (cited authors)

  • Pradhan, G., Wu, C., Villarreal, D., Lee, J. H., Han, H. W., Gaharwar, A., ... Sun, Y.

citation count

  • 10

complete list of authors

  • Pradhan, Geetali||Wu, Chia-Shan||Villarreal, Daniel||Lee, Jong Han||Han, Hye Won||Gaharwar, Akhilesh||Tian, Yanan||Fu, Wenxian||Guo, Shaodong||Smith, Roy G||Sun, Yuxiang

publication date

  • April 2021