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

Lobner, Kristian and Steinbrenner, Holger and Roberts, Graham A and Ling, Zhidong and Huang, Guo-Cai and Piquer, Sandra and Pipeleers, Daniel G and 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...

Full text not available from this repository.

Item Type:Article
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
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

Repository Staff Only: item control page