A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis.

Malin Fex, G Haemmerle, Nils Wierup, Marloes Dekker Nitert, M Rehn, M Ristow, R Zechner, Frank Sundler, Cecilia Holm, L Eliasson, Hindrik Mulder

Research output: Contribution to journalArticlepeer-review

35 Citations (SciVal)

Abstract

AIMS/HYPOTHESIS: The enzyme hormone-sensitive lipase (HSL) is produced and is active in pancreatic beta cells. Because lipids are known to play a crucial role in normal control of insulin release and in the deterioration of beta cell function, as observed in type 2 diabetes, actions of HSL in beta cells may be critical. This notion has been addressed in different lines of HSL knockout mice with contradictory results. METHODS: To resolve this, we created a transgenic mouse lacking HSL specifically in beta cells, and characterised this model with regard to glucose metabolism and insulin secretion, using both in vivo and in vitro methods. RESULTS: We found that fasting basal plasma glucose levels were significantly elevated in mice lacking HSL in beta cells. An IVGTT at 12 weeks revealed a blunting of the initial insulin response to glucose with delayed elimination of the sugar. Additionally, arginine-stimulated insulin secretion was markedly diminished in vivo. Investigation of the exocytotic response in single HSL-deficient beta cells showed an impaired response to depolarisation of the plasma membrane. Beta cell mass and islet insulin content were increased, suggesting a compensatory mechanism, by which beta cells lacking HSL strive to maintain normoglycaemia. CONCLUSIONS/INTERPRETATION: Based on these results, we suggest that HSL, which is located in close proximity of the secretory granules, may serve as provider of a lipid-derived signal essential for normal insulin secretion.
Original languageEnglish
Pages (from-to)271-280
JournalDiabetologia
Volume52
DOIs
Publication statusPublished - 2009

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Diabetes and Celiac Unit (013241540), Molecular Endocrinology (013212018), Molecular Metabolism (013212001), Diabetes and Endocrinology (013241530), Neuroendocrine Cell Biology (013212008)

Subject classification (UKÄ)

  • Endocrinology and Diabetes

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