Sphingosine-1-phosphate as a key player of insulin secretion induced by high-density lipoprotein treatment.

Autor:	Brulhart-Meynet MC; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland., Thomas A; Unit of Toxicology, University Centre of Legal Medicine, Lausanne-Geneva, Switzerland., Sidibé J; Unit of Toxicology, University Centre of Legal Medicine, Lausanne-Geneva, Switzerland., Visentin F; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland., Dusaulcy R; Pediatric Endocrine and Diabetes Unit, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Geneva, Switzerland., Schwitzgebel V; Pediatric Endocrine and Diabetes Unit, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Geneva, Switzerland., Pataky Z; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland., Philippe J; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland., Vuilleumier N; Division of Laboratory Medicine, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland.; Department of Medicine, Medical Faculty, Geneva University, Geneva, Switzerland., James RW; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland., Gosmain Y; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland., Frias MA; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.; Division of Laboratory Medicine, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland.; Department of Medicine, Medical Faculty, Geneva University, Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Physiological reports [Physiol Rep] 2021 Mar; Vol. 9 (6), pp. e14786.
DOI:	10.14814/phy2.14786
Abstrakt:	Beta cell failure is one of the most important features of type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) has been proposed to improve β-cell function. However, the mechanisms involved in this process are still poorly understood. The aim of this study was to investigate the contribution of sphingosine-1-phosphate (S1P) in the impact of HDL treatment on insulin secretion by pancreatic β-cells and to determine its mechanisms. Primary cultures of β-cells isolated from rat were treated with or without HDL in the presence or absence of S1P pathway inhibitors and insulin secretion response was analyzed. The S1P content of HDL (HDL-S1P) isolated from T2DM patients was analyzed and correlated to the HDL-induced insulin secretion. The expression of genes involved in the biosynthesis of the insulin was also evaluated. HDL as well as S1P treatment enhanced glucose-stimulated insulin secretion (GSIS). In HDL isolated from T2DM patients, while HDL-S1P was strongly correlated to its pro-secretory capacity (r = 0.633, p = 0.005), HDL-cholesterol and apolipoprotein AI levels were not. HDL-induced GSIS was blocked by the S1P1/3 antagonist but not by the S1P2 antagonist, and was also accompanied by increased intracellular S1P in β-cells. We also observed that HDL improved GSIS without significant changes in expression levels of insulin biosynthesis genes. Our present study highlights the importance HDL-S1P in GSIS in T2DM patients and demonstrates that HDL induces insulin secretion by a process involving both intra- and extra-cellular sources of S1P independently of an effect on insulin biosynthesis genes. (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
Databáze:	MEDLINE
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