Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion
| Autor: | Michael W. Adams, Cynthia J. Donaldson, Kevin L. Grove, Christopher Cowing-Zitron, Talitha van der Meulen, Lynley D. Pound, Mark O. Huising, Andreas Zembrzycki, Anna E. Hunter, Elena L. Caceres |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_treatment Biological sciences/Physiology/Metabolism/Metabolic diseases/Diabetes/Type 2 diabetes Health sciences/Diseases/Endocrine system and metabolic diseases/Diabetes/Type 2 diabetes Inbred C57BL Medical and Health Sciences Mice Diabetes mellitus genetics 0302 clinical medicine Models Insulin-Secreting Cells Insulin Secretion Insulin Child Receptor Urocortins Feedback Physiological 0303 health sciences Chemistry General Medicine Middle Aged Tissue Donors 3. Good health Insulin oscillation Somatostatin Child Preschool Female Adult medicine.medical_specialty Adolescent Somatostatin secretion Physiological Immunology Health sciences/Endocrinology 030209 endocrinology & metabolism Models Biological Article General Biochemistry Genetics and Molecular Biology Feedback Young Adult 03 medical and health sciences Internal medicine Paracrine Communication Diabetes Mellitus medicine Animals Humans Preschool Metabolic and endocrine Aged 030304 developmental biology Delta cell Infant Newborn Infant Biological Newborn Mice Inbred C57BL HEK293 Cells Endocrinology Gene Expression Regulation Hyperglycemia Macaca Transcriptome Homeostasis Biological sciences/Physiology/Metabolism/Homeostasis |
| Zdroj: | Nature medicine, vol 21, iss 7 Van Der Meulen, T; Donaldson, CJ; Cáceres, E; Hunter, AE; Cowing-Zitron, C; Pound, LD; et al.(2015). Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nature Medicine, 21(7), 769-776. doi: 10.1038/nm.3872. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/63r225dj Nature medicine |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm.3872 |
| Popis: | © 2015 Nature America, Inc. All rights reserved. The peptide hormone urocortin3 (Ucn3) is abundantly expressed by mature beta cells, yet its physiological role is unknown. Here we demonstrate that Ucn3 is stored and co-released with insulin and potentiates glucose-stimulated somatostatin secretion via cognate receptors on delta cells. Further, we found that islets lacking endogenous Ucn3 have fewer delta cells, reduced somatostatin content, impaired somatostatin secretion, and exaggerated insulin release, and that these defects are rectified by treatment with synthetic Ucn3 in vitro. Our observations indicate that the paracrine actions of Ucn3 activate a negative feedback loop that promotes somatostatin release to ensure the timely reduction of insulin secretion upon normalization of plasma glucose. Moreover, Ucn3 is markedly depleted from beta cells in mouse and macaque models of diabetes and in human diabetic islets. This suggests that Ucn3 is a key contributor to stable glycemic control, whose reduction during diabetes aggravates glycemic volatility and contributes to the pathophysiology of this disease. |
| Databáze: | OpenAIRE |
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