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Article

β Cell GHS-R Regulates Insulin Secretion and Sensitivity

1
USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
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Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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Department of Nutrition, Texas A&M University, College Station, TX 77843, USA
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Department of Marine Bioindustry, Hanseo University, Seosan 31962, Korea
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Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA
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Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA
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Department of Pediatrics, University of California, San Diego, CA 92161, USA
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Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Maria Elisabeth Street, Paolo Moghetti and Francesco Chiarelli
Int. J. Mol. Sci. 2021, 22(8), 3950; https://doi.org/10.3390/ijms22083950
Received: 16 March 2021 / Revised: 9 April 2021 / Accepted: 9 April 2021 / Published: 11 April 2021
(This article belongs to the Special Issue Insulin Sensitivity/Resistance: From Physiology to Disease)
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 β and α cells. We then generated β-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 β and α cells; GHS-R cell-autonomously regulated GSIS and modulated systemic insulin sensitivity. In conclusion, β cell GHS-R was an important regulator of glucose homeostasis, and GHS-R antagonists may have therapeutic potential for Type 2 Diabetes. View Full-Text
Keywords: growth hormone secretagogue receptor (GHS-R); glucose-stimulated insulin secretion (GSIS); MIP-Cre/ERT; pancreatic islets; β cells; insulin secretion; insulin sensitivity growth hormone secretagogue receptor (GHS-R); glucose-stimulated insulin secretion (GSIS); MIP-Cre/ERT; pancreatic islets; β cells; insulin secretion; insulin sensitivity
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MDPI and ACS Style

Pradhan, G.; Wu, C.-S.; Villarreal, D.; Lee, J.H.; Han, H.W.; Gaharwar, A.; Tian, Y.; Fu, W.; Guo, S.; Smith, R.G.; Sun, Y. β Cell GHS-R Regulates Insulin Secretion and Sensitivity. Int. J. Mol. Sci. 2021, 22, 3950. https://doi.org/10.3390/ijms22083950

AMA Style

Pradhan G, Wu C-S, Villarreal D, Lee JH, Han HW, Gaharwar A, Tian Y, Fu W, Guo S, Smith RG, Sun Y. β Cell GHS-R Regulates Insulin Secretion and Sensitivity. International Journal of Molecular Sciences. 2021; 22(8):3950. https://doi.org/10.3390/ijms22083950

Chicago/Turabian Style

Pradhan, Geetali, Chia-Shan Wu, Daniel Villarreal, Jong H. Lee, Hye W. Han, Akhilesh Gaharwar, Yanan Tian, Wenxian Fu, Shaodong Guo, Roy G. Smith, and Yuxiang Sun. 2021. "β Cell GHS-R Regulates Insulin Secretion and Sensitivity" International Journal of Molecular Sciences 22, no. 8: 3950. https://doi.org/10.3390/ijms22083950

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