The expression of hormone-sensitive lipase in clonal β-cells and rat islets is induced by long-term exposure to high glucose

MS Winzell, H Svensson, P Arner, B Ahrén, C Holm - Diabetes, 2001 - Am Diabetes Assoc
MS Winzell, H Svensson, P Arner, B Ahrén, C Holm
Diabetes, 2001Am Diabetes Assoc
Hormone-sensitive lipase (HSL) is expressed and enzymatically active in β-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 …
Hormone-sensitive lipase (HSL) is expressed and enzymatically active in β-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 ∼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 ∼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 β-cell responses to hyperglycemia and also in generating the lipid signal that is needed in stimulus-secretion coupling.
Am Diabetes Assoc