The expression of hormone-sensitive lipase in clonal beta-cells and rat islets is induced by long-term exposure to high glucose
(2001) In Diabetes 50(10). p.2225-2230- Abstract
- Hormone-sensitive lipase (HSL) is expressed and enzymatically active in beta-cells and has been proposed to be involved in the generation of the lipid-derived signal that seems to be necessary for glucose-stimulated insulin secretion. In this study, we investigated whether the expression of HSL in INS-1 cells and in rat islets is affected by exposure to high glucose concentrations. Incubation of INS-1 cells in 25 mmol/l glucose for 16 and 32 h induced HSL protein expression twofold, whereas no effect was observed after 4 and 8 h of incubation. The HSL activity, defined as the diglyceride lipase activity inhibited by anti-rat HSL antibodies, constituted approximately 25% of total diglyceride lipase activity and was induced to a similar... (More)
- Hormone-sensitive lipase (HSL) is expressed and enzymatically active in beta-cells and has been proposed to be involved in the generation of the lipid-derived signal that seems to be necessary for glucose-stimulated insulin secretion. In this study, we investigated whether the expression of HSL in INS-1 cells and in rat islets is affected by exposure to high glucose concentrations. Incubation of INS-1 cells in 25 mmol/l glucose for 16 and 32 h induced HSL protein expression twofold, whereas no effect was observed after 4 and 8 h of incubation. The HSL activity, defined as the diglyceride lipase activity inhibited by anti-rat HSL antibodies, constituted approximately 25% of total diglyceride lipase activity and was induced to a similar extent as HSL protein levels. The glucose effect at 16 h on HSL protein expression level was confirmed in freshly isolated rat islets. Exposure of INS-1 cells to different glucose concentrations for 16 h showed that the inductive effect on HSL protein levels was maximum at 20 mmol/l glucose (2- to 2.5-fold). Northern blot analysis demonstrated a more than threefold elevation of HSL mRNA levels. The induction was blocked by actinomycin D, and the half-life of the transcript seemed to be unchanged by high glucose, suggesting a transcriptional nature of the glucose effect on HSL gene expression. The nonmetabolizable glucose analog 2-deoxyglucose, which has no mitogenic effect, induced HSL approximately 1.3-fold, whereas mannose was similar to glucose, stimulating HSL expression 1.7- to 2-fold. The results suggest that HSL is involved in the beta-cell responses to hyperglycemia and also in generating the lipid signal that is needed in stimulus-secretion coupling. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1120827
- author
- Winzell, M S ; Svensson, H ; Arner, P ; Ahren, B and Holm, Cecilia LU
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 50
- issue
- 10
- pages
- 2225 - 2230
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- pmid:11574402
- ISSN
- 1939-327X
- language
- English
- LU publication?
- yes
- id
- d63a054c-dfe7-4d78-994c-6543142f8a11 (old id 1120827)
- alternative location
- http://diabetes.diabetesjournals.org/cgi/content/full/50/10/2225
- date added to LUP
- 2016-04-01 16:54:39
- date last changed
- 2018-11-21 20:45:10
@article{d63a054c-dfe7-4d78-994c-6543142f8a11,
abstract = {{Hormone-sensitive lipase (HSL) is expressed and enzymatically active in beta-cells and has been proposed to be involved in the generation of the lipid-derived signal that seems to be necessary for glucose-stimulated insulin secretion. In this study, we investigated whether the expression of HSL in INS-1 cells and in rat islets is affected by exposure to high glucose concentrations. Incubation of INS-1 cells in 25 mmol/l glucose for 16 and 32 h induced HSL protein expression twofold, whereas no effect was observed after 4 and 8 h of incubation. The HSL activity, defined as the diglyceride lipase activity inhibited by anti-rat HSL antibodies, constituted approximately 25% of total diglyceride lipase activity and was induced to a similar extent as HSL protein levels. The glucose effect at 16 h on HSL protein expression level was confirmed in freshly isolated rat islets. Exposure of INS-1 cells to different glucose concentrations for 16 h showed that the inductive effect on HSL protein levels was maximum at 20 mmol/l glucose (2- to 2.5-fold). Northern blot analysis demonstrated a more than threefold elevation of HSL mRNA levels. The induction was blocked by actinomycin D, and the half-life of the transcript seemed to be unchanged by high glucose, suggesting a transcriptional nature of the glucose effect on HSL gene expression. The nonmetabolizable glucose analog 2-deoxyglucose, which has no mitogenic effect, induced HSL approximately 1.3-fold, whereas mannose was similar to glucose, stimulating HSL expression 1.7- to 2-fold. The results suggest that HSL is involved in the beta-cell responses to hyperglycemia and also in generating the lipid signal that is needed in stimulus-secretion coupling.}},
author = {{Winzell, M S and Svensson, H and Arner, P and Ahren, B and Holm, Cecilia}},
issn = {{1939-327X}},
language = {{eng}},
number = {{10}},
pages = {{2225--2230}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{The expression of hormone-sensitive lipase in clonal beta-cells and rat islets is induced by long-term exposure to high glucose}},
url = {{http://diabetes.diabetesjournals.org/cgi/content/full/50/10/2225}},
volume = {{50}},
year = {{2001}},
}