Lobner, Kristian, Steinbrenner, Holger, Roberts, Graham A , Ling, Zhidong, Huang, Guo-Cai, Piquer, Sandra, Pipeleers, Daniel G, Seissler, Jochen and Christie, Michael R. (2002) Different regulated expression of the tyrosine phosphatase-like proteins IA-2 and phogrin by glucose and insulin in pancreatic islets. Relationship to development of insulin secretory responses in early life. Diabetes, 51 (10). pp. 2982-2988. ISSN 0012-1797
Full content URL: http://diabetes.diabetesjournals.org/content/51/10...
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Item Type: | Article |
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Item Status: | Live Archive |
Abstract
IA-2 and phogrin are tyrosine phosphatase-like proteins that may mediate interactions between secretory granules and cytoskeleton in islets and neuroendocrine tissues. We investigated factors that regulate IA-2 and phogrin expression and their relationship to maturation of insulin secretory responses that occur after birth. Islet content of IA-2, but not phogrin, increased during the first 10 days of life in rats, when insulin secretion in response to glucose increased to adult levels. In cultured 5-day-old rat islets, IA-2 protein and mRNA was increased by glucose and agents that potentiate insulin secretion by the cAMP pathway. Addition of insulin increased IA-2 protein levels and insulin biosynthesis without affecting IA-2 mRNA. Blocking insulin secretion with diazoxide or insulin action with insulin receptor antibodies inhibited glucose-induced increases in IA-2 protein, but not those of mRNA. Phogrin expression was unchanged by all agents. Thus, IA-2 is regulated at the mRNA level by glucose and elevated cAMP, whereas locally secreted insulin modulates IA-2 protein levels by stimulating biosynthesis. In contrast, phogrin expression is insensitive to factors that modify β-cell function. These results demonstrate differential regulation of two closely related secretory granule components and identify IA-2 as a granule membrane protein subject to autocrine regulation by insulin.
Keywords: | Pancreatic islets, Diabetes, Insulin, Development |
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Subjects: | B Subjects allied to Medicine > B100 Anatomy, Physiology and Pathology C Biological Sciences > C130 Cell Biology C Biological Sciences > C141 Developmental Biology |
Divisions: | College of Science > School of Life Sciences |
ID Code: | 19806 |
Deposited On: | 12 Dec 2015 21:40 |
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