A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis.
(2009) In Diabetologia 52. p.271-280- 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... (More)
- 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. (Less)
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https://lup.lub.lu.se/record/1271230
- author
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetologia
- volume
- 52
- pages
- 271 - 280
- publisher
- Springer
- external identifiers
-
- wos:000262411200013
- pmid:19023560
- scopus:58149473940
- pmid:19023560
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-008-1191-9
- language
- English
- LU publication?
- yes
- additional info
- 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)
- id
- e98bfc04-6dfd-435c-899e-55a164ca29f0 (old id 1271230)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19023560?dopt=Abstract
- date added to LUP
- 2016-04-04 08:49:04
- date last changed
- 2024-04-12 23:05:07
@article{e98bfc04-6dfd-435c-899e-55a164ca29f0, 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.}}, author = {{Fex, Malin and Haemmerle, G and Wierup, Nils and Dekker Nitert, Marloes and Rehn, M and Ristow, M and Zechner, R and Sundler, Frank and Holm, Cecilia and Eliasson, L and Mulder, Hindrik}}, issn = {{1432-0428}}, language = {{eng}}, pages = {{271--280}}, publisher = {{Springer}}, series = {{Diabetologia}}, title = {{A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis.}}, url = {{http://dx.doi.org/10.1007/s00125-008-1191-9}}, doi = {{10.1007/s00125-008-1191-9}}, volume = {{52}}, year = {{2009}}, }