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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

Inhibition of lipase activity and lipolysis in rat islets reduces insulin secretion.

Author

  • Hindrik Mulder
  • Shumin Yang
  • Maria Sörhede Winzell
  • Cecilia Holm
  • Bo Ahrén

Summary, in English

Lipids may serve as coupling factors in KATP-independent glucose sensing in β-cells. We have previously demonstrated that β-cells harbor lipase activities, one of which is the hormone-sensitive lipase. Whether β-cell lipases are critical for glucose-stimulated insulin secretion (GSIS) by providing lipid-derived signals from endogenous lipids is unknown. Therefore, using a lipase inhibitor (orlistat), we examined whether lipase inhibition reduces insulin secretion. Islet lipolysis stimulated by glucose and diglyceride lipase activity was abolished by orlistat. Incubation of rat islets with orlistat dose dependently inhibited GSIS; this inhibition was reversed by 1 mmol/l palmitate, suggesting that orlistat acts via impaired formation of an acylglyceride-derived coupling signal. Orlistat inhibited the potentiating effect of forskolin on GSIS, an effect proposed to be due to activation of a lipase. In perifused islets, orlistat attenuated mainly the second phase of insulin secretion. Because the rise in islet ATP/ADP levels in response to glucose and oxidation of the sugar were unaffected by orlistat whereas the second phase of insulin secretion was reduced, it seems likely that a lipid coupling factor involved in KATP-independent glucose sensing has been perturbed. Thus, β-cell lipase activity is involved in GSIS, emphasizing the important role of β-cell lipid metabolism for insulin secretion.

Department/s

  • Diabetes - Molecular Metabolism
  • Medicine, Lund
  • Molecular Endocrinology

Publishing year

2004

Language

English

Pages

122-128

Publication/Series

Diabetes

Volume

53

Issue

1

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Molecular Metabolism
  • Molecular Endocrinology

ISBN/ISSN/Other

  • ISSN: 1939-327X