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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact.

Author

  • Hindrik Mulder
  • Maria Sorhede-Winzell
  • Juan Antonio Contreras
  • Malin Fex
  • Kristoffer Strom
  • Thorkil Ploug
  • Henrik Galbo
  • Peter Arner
  • Cecilia Lundberg
  • Frank Sundler
  • Bo Ahrén
  • Cecilia Holm

Summary, in English

Lipid metabolism plays an important role in glucose homeostasis under normal and pathological conditions. In adipocytes, skeletal muscle, and pancreatic beta-cells, lipids are mobilized from acylglycerides by the hormone-sensitive lipase (HSL). Here, the consequences of a targeted disruption of the HSL gene for glucose homeostasis were examined. HSL null mice were slightly hyperglycemic in the fasted, but not fed state, which was accompanied by moderate hyperinsulinemia. During glucose challenges, however, disposal of the sugar was not affected in HSL null mice, presumably because of release of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance. Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia.

Department/s

  • Diabetes - Molecular Metabolism
  • Department of Experimental Medical Science
  • Diabetes and Celiac Unit
  • Medicine, Lund
  • Molecular Endocrinology

Publishing year

2003

Language

English

Pages

36380-36388

Publication/Series

Journal of Biological Chemistry

Volume

278

Issue

38

Document type

Journal article

Publisher

ASBMB

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Diabetes - Molecular Metabolism
  • Diabetes and Celiac Unit
  • Molecular Endocrinology

ISBN/ISSN/Other

  • ISSN: 1083-351X