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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

CaV1.2 rather than CaV1.3 is coupled to glucose-stimulated insulin secretion in INS-1 832/13 cells.

Author

  • Marloes Dekker Nitert
  • Cecilia Nagorny
  • Anna Wendt
  • Lena Eliasson
  • Hindrik Mulder

Summary, in English

In clonal beta-cell lines and islets from different species, a variety of calcium channels are coupled to glucose-stimulated insulin secretion. The aim of this study was to identify the voltage-gated calcium channels that control insulin secretion in insulinoma (INS)-1 832/13 cells. The mRNA level of Ca(V)1.2 exceeded that of Ca(V)1.3 and Ca(V)2.3 two-fold. Insulin secretion, which rose tenfold in response to 16.7 mM glucose, was completely abolished by 5 microM isradipine that blocks Ca(V)1.2 and Ca(V)1.3. Similarly, the increase in intracellular calcium in response to 15 mM glucose was decreased in the presence of 5 microM isradipine, and the frequency of calcium spikes was decreased to the level seen at 2.8 mM glucose. By contrast, inhibition of Ca(V)2.3 with 100 nM SNX-482 did not significantly affect insulin secretion or intracellular calcium. Using RNA interference, Ca(V)1.2 mRNA and protein levels were knocked down by approximately 65% and approximately 34% respectively, which reduced insulin secretion in response to 16.7 mM glucose by 50%. Similar reductions in calcium currents and cell capacitance were seen in standard whole-cell patch-clamp experiments. The remaining secretion of insulin could be reduced to the basal level by 5 microM isradipine. Calcium influx underlying this residual insulin secretion could result from persisting Ca(V)1.2 expression in transfected cells since knock-down of Ca(V)1.3 did not affect glucose-stimulated insulin secretion. In summary, our results suggest that Ca(V)1.2 is critical for insulin secretion in INS-1 832/13 cells.

Department/s

  • Department of Clinical Sciences, Malmö
  • Diabetes - Molecular Metabolism

Publishing year

2008

Language

English

Pages

1-11

Publication/Series

Journal of Molecular Endocrinology

Volume

41

Issue

1

Document type

Journal article

Publisher

Society for Endocrinology

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Molecular Metabolism

ISBN/ISSN/Other

  • ISSN: 1479-6813