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> (2000-2004)
> Medical and Health Sciences
> Winzell M. S. >
The expression of h...
The expression of hormone-sensitive lipase in clonal beta-cells and rat islets is induced by long-term exposure to high glucose
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Winzell, M S (author)
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Svensson, H (author)
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- Arner, P (author)
- Karolinska Institutet
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Ahren, B (author)
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- Holm, Cecilia (author)
- Lund University,Lunds universitet,Molekylär endokrinologi,Forskargrupper vid Lunds universitet,Molecular Endocrinology,Lund University Research Groups
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(creator_code:org_t)
- American Diabetes Association, 2001
- 2001
- English.
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 50:10, s. 2225-2230
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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