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Diabetes 51:2982-2988, 2002
© 2002 by the American Diabetes Association, Inc.

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

Kristian Löbner1, Holger Steinbrenner2, Graham A. Roberts1, Zhidong Ling3, Guo-Cai Huang1, Sandra Piquer4, Daniel G. Pipeleers3, Jochen Seissler2, and Michael R. Christie1

1 Department of Medicine, Guy’s, King’s and St. Thomas’s School of Medicine, King’s College London, London, U.K.
2 German Diabetes Research Centre, University of Düsseldorf, Düsseldorf, Germany
3 Diabetes Research Center, Free University of Brussels (VUB), Brussels, Belgium
4 Department of Medicine, San Raffaele Institute, Milan, Italy

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 ß-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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S.-i. Harashima, A. Clark, M. R. Christie, and A. L. Notkins
The dense core transmembrane vesicle protein IA-2 is a regulator of vesicle number and insulin secretion
PNAS, June 14, 2005; 102(24): 8704 - 8709.
[Abstract] [Full Text] [PDF]


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Copyright © 2002 by the American Diabetes Association.