Acyl-ghrelin Is Permissive for the Normal Counterregulatory Response to Insulin-Induced Hypoglycemia
| العنوان: | Acyl-ghrelin Is Permissive for the Normal Counterregulatory Response to Insulin-Induced Hypoglycemia |
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| المؤلفون: | Brianna G. Findley, Deepali Gupta, Chen Liu, Bharath K. Mani, Eric D. Berglund, Jeffrey M. Zigman, Sherri Osborne-Lawrence, Kripa Shankar, Claudio Pietra, Caleb C. Lord, Nathan P. Metzger |
| المصدر: | Diabetes |
| بيانات النشر: | American Diabetes Association, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Complications, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Growth hormone secretagogue receptor, 030209 endocrinology & metabolism, Hypoglycemia, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Corticosterone, Internal medicine, Internal Medicine, medicine, Animals, Insulin, Receptors, Ghrelin, Receptor, Mice, Knockout, business.industry, digestive, oral, and skin physiology, Glucose clamp technique, medicine.disease, Ghrelin, Mice, Inbred C57BL, Neuroprotective Agents, 030104 developmental biology, Endocrinology, chemistry, Glucose Clamp Technique, business, Hormone |
| الوصف: | Insulin-induced hypoglycemia leads to far-ranging negative consequences in patients with diabetes. Components of the counterregulatory response (CRR) system that help minimize and reverse hypoglycemia and coordination between those components are well studied but not yet fully characterized. Here, we tested the hypothesis that acyl-ghrelin, a hormone that defends against hypoglycemia in a preclinical starvation model, is permissive for the normal CRR to insulin-induced hypoglycemia. Ghrelin knockout (KO) mice and wild-type (WT) littermates underwent an insulin bolus-induced hypoglycemia test and a low-dose hyperinsulinemic-hypoglycemic clamp procedure. Clamps also were performed in ghrelin-KO mice and C57BL/6N mice administered the growth hormone secretagogue receptor agonist HM01 or vehicle. Results show that hypoglycemia, as induced by an insulin bolus, was more pronounced and prolonged in ghrelin-KO mice, supporting previous studies suggesting increased insulin sensitivity upon ghrelin deletion. Furthermore, during hyperinsulinemic-hypoglycemic clamps, ghrelin-KO mice required a 10-fold higher glucose infusion rate (GIR) and exhibited less robust corticosterone and growth hormone responses. Conversely, HM01 administration, which reduced the GIR required by ghrelin-KO mice during the clamps, increased plasma corticosterone and growth hormone. Thus, our data suggest that endogenously produced acyl-ghrelin not only influences insulin sensitivity but also is permissive for the normal CRR to insulin-induced hypoglycemia. |
| تدمد: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db19-0438 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0857976820af535c39ddd9f51bbd7c8d https://doi.org/10.2337/db19-0438 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0857976820af535c39ddd9f51bbd7c8d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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| DOI: | 10.2337/db19-0438 |