Exp Clin Endocrinol Diabetes 2003; 111(6): 358-363
DOI: 10.1055/s-2003-42727
Article

J. A. Barth Verlag in Georg Thieme Verlag Stuttgart · New York

Direct Comparison of Inositol Phosphoglycan with Prostaglandylinositol Cyclic Phosphate, Two Potential Mediators of Insulin Action

H. K. Wasner 1 , G. Müller 2 , J. Eckel 1
  • 1Deutsches Diabetes-Forschungsinstitut, Abteilung für klinische Biochemie und Pathobiochemie, Düsseldorf, Germany
  • 2Aventis Pharma Deutschland GmbH, Frankfurt am Main, Germany
Further Information

Publication History

Received: August 13, 2002 First decision: October 14, 2002

Accepted: February 11, 2003

Publication Date:
01 October 2003 (online)

Abstract

Though insulin signalling is thought by many groups to function without second messenger action, others have provided evidence for the existence and action of such regulators. Chemically quite different compounds, however, have been proposed as mediators, such as various inositol phosphoglycans and prostaglandylinositol cyclic phosphate (cyclic PIP). In spite of marked structural differences, these compounds are reported to have the same regulatory properties, i.e. to activate protein ser/thr phosphatases and to inhibit protein kinase A. In order to clarify this discrepancy, the regulatory potency of these different compounds was assayed under identical conditions. It was found that in contrast to cyclic PIP, the synthetic inositol phosphoglycan PIG41 neither directly inhibited protein kinase A nor activated protein ser/thr phosphatases. However, when added to intact cells, such as primary adipocytes, PIG41 inhibited isoproterenol-stimulated lipolysis. This effect most likely results from tyrosine phosphorylation of insulin receptor substrates (IRSs) by PIG41. This tyrosine phosphorylation is not carried out by the insulin receptor tyrosine kinase but by cytosolic tyrosine kinases. This indicates that cyclic PIP, an intracellular regulator, which primarily acts on protein kinase A and on protein ser/thr phosphatases, operates more downstream in the signal transduction cascade as compared to the inositol phosphoglycan PIG41. Thus, cyclic PIP appears to be a suitable candidate to close the gap between IRSs and the protein kinases/phosphatases involved in the signal transduction of insulin.

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Dr. H. K. Wasner

Deutsches Diabetes-Forschungsinstitut

Auf'm Hennekamp 65

40225 Düsseldorf

Germany

Phone: + 492113382622

Fax: + 49 21 13 38 26 03

Email: heinrich.wasner@ddfi.uni-duesseldorf.de

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