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

Fex, M., Haemmerle, G., Wierup, N., Dekker-Nitert, M., Rehn, M., Ristow, M., Zechner, R., Sundler, F., Holm, C., Eliasson, L. and Mulder, H. (2009) A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis. Diabetologia, 52 2: 271-280.


Author Fex, M.
Haemmerle, G.
Wierup, N.
Dekker-Nitert, M.
Rehn, M.
Ristow, M.
Zechner, R.
Sundler, F.
Holm, C.
Eliasson, L.
Mulder, H.
Title A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis
Journal name Diabetologia   Check publisher's open access policy
ISSN 0012-186X
1432-0428
Publication date 2009-02
Sub-type Article (original research)
DOI 10.1007/s00125-008-1191-9
Volume 52
Issue 2
Start page 271
End page 280
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Formatted 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.

Keyword Beta cell mass
Insulin secretion
Lipid coupling factor
Membrane capacitance
Stimulated Insulin-Secretion
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 18 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 142 Abstract Views  -  Detailed Statistics
Created: Tue, 20 Sep 2011, 13:57:33 EST by System User on behalf of Royal Brisbane Clinical School