Different Regulated Expression of the Tyrosine Phosphatase-Like Proteins IA-2 and Phogrin by Glucose and Insulin in Pancreatic Islets

Diabetes - Tập 51 Số 10 - Trang 2982-2988 - 2002
Kristian Löbner1, Holger Steinbrenner2, Graham Roberts1, Zhidong Ling3, Guo-Cai Huang1, Sandra Piquer4, Daniël Pipeleers3, Jochen Seißler2, Michael R. Christie1
1Department of Medicine, Guy's, King's and St. Thomas's School of Medicine, King's College London, London, U.K.
2German Diabetes Research Centre, University of Düsseldorf, Düsseldorf, Germany
3Diabetes Research Center, Free University of Brussels (VUB), Brussels, Belgium
4Department of Medicine, San Raffaele Institute, Milan, Italy

Tóm tắt

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.

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