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Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

Important role of phosphodiesterase 3B for the stimulatory action of cAMP on pancreatic beta -cell exocytosis and release of insulin.

Author

  • Linda Härndahl
  • Xingjun Jing
  • Rosita Ivarsson
  • Eva Degerman
  • Bo Ahrén
  • Vincent C. Manganiello
  • Erik Renström
  • Lena Stenson Holst

Summary, in English

Cyclic AMP potentiates glucose-stimulated insulin release and mediates the stimulatory effects of hormones such as glucagon-like peptide 1 (GLP-1) on pancreatic b-cells. By inhibition of cAMP-degrading phosphodiesterase (PDE) and, in particular, selective inhibition of PDE3 activity, stimulatory effects on insulin secretion have been observed. Molecular and functional information on b-cell PDE3 is, however, scarce. To provide such information, we have studied the specific effects of the PDE3B isoform by adenovirus-mediated overexpression. In rat islets and rat insulinoma cells, approximate 10-fold overexpression of PDE3B was accompanied by a 6-8-fold increase in membrane-associated PDE3B activity. The cAMP concentration was significantly lowered in transduced cells (INS-1(832/13), and insulin secretion in response to stimulation with high glucose (11.1 mM) was reduced by 40% (islets) and 50% (INS-1). Further, the ability of GLP-1 (100 nM) to augment glucose-stimulated insulin secretion was inhibited by approximately 30% (islets) and 70% (INS-1). Accordingly, when stimulating with cAMP, a substantial decrease (65%) in exocytotic capacity was demonstrated in patch-clamped single b-cells. In untransduced insulinoma cells, application of the PDE3-selective inhibitor OPC3911 (10 mM) was shown to increase glucose-stimulated insulin release as well as cAMP-enhanced exocytosis. The findings suggest a significant role of PDE3B as an important regulator of insulin secretory processes.

Department/s

  • Department of Experimental Medical Science
  • Diabetes - Islet Patophysiology
  • Neurosurgery
  • Insulin Signal Transduction
  • Medicine, Lund

Publishing year

2002

Language

English

Pages

37446-37455

Publication/Series

Journal of Biological Chemistry

Volume

277

Issue

40

Document type

Journal article

Publisher

ASBMB

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Insulin Signal Transduction

ISBN/ISSN/Other

  • ISSN: 1083-351X