Lysophosphatidylinositols Are Upregulated After Human β-Cell Loss and Potentiate Insulin Release.

Autor:	Jiménez-Sánchez C; Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.; Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland.; Department of Surgery, Geneva University Hospitals, Geneva, Switzerland., Sinturel F; Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.; Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland.; Department of Surgery, Geneva University Hospitals, Geneva, Switzerland., Mezza T; Pancreas Unit, Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli, Institute of Hospitalization and Scientific Care (IRCCS), Rome, Italy.; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy., Loizides-Mangold U; Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.; Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland.; Department of Surgery, Geneva University Hospitals, Geneva, Switzerland., Montoya JP; Proteomics Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Li L; Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.; Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland., Di Giuseppe G; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.; Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy., Quero G; Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.; Chirurgia Digestiva, Fondazione Policlinico Universitario Gemelli IRCSS Università Cattolica del Sacro Cuore, Rome, Italy., Guessous I; Department of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland., Jornayvaz F; Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland.; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland., Schrauwen P; Department of Nutrition and Movement Sciences, Maastricht University Medical Center, Maastricht, the Netherlands., Stenvers DJ; Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.; Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, the Netherlands., Alfieri S; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.; Chirurgia Digestiva, Fondazione Policlinico Universitario Gemelli IRCSS Università Cattolica del Sacro Cuore, Rome, Italy., Giaccari A; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.; Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy., Berishvili E; Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland.; Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.; Cell isolation and Transplantation Center, Geneva University Hospitals, Geneva, Switzerland., Compagnon P; Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.; Cell isolation and Transplantation Center, Geneva University Hospitals, Geneva, Switzerland., Bosco D; Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland.; Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.; Cell isolation and Transplantation Center, Geneva University Hospitals, Geneva, Switzerland., Riezman H; Department of Biochemistry, Faculty of Science, National Centre of Competence in Research Chemical Biology, University of Geneva, Geneva, Switzerland., Dibner C; Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.; Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland.; Department of Surgery, Geneva University Hospitals, Geneva, Switzerland., Maechler P; Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.; Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2024 Jan 01; Vol. 73 (1), pp. 93-107.
DOI:	10.2337/db23-0205
Abstrakt:	In this study, we identified new lipid species associated with the loss of pancreatic β-cells triggering diabetes. We performed lipidomics measurements on serum from prediabetic mice lacking β-cell prohibitin-2 (a model of monogenic diabetes) patients without previous history of diabetes but scheduled for pancreaticoduodenectomy resulting in the acute reduction of their β-cell mass (∼50%), and patients with type 2 diabetes (T2D). We found lysophosphatidylinositols (lysoPIs) were the main circulating lipid species altered in prediabetic mice. The changes were confirmed in the patients with acute reduction of their β-cell mass and in those with T2D. Increased lysoPIs significantly correlated with HbA1c (reflecting glycemic control), fasting glycemia, and disposition index, and did not correlate with insulin resistance or obesity in human patients with T2D. INS-1E β-cells as well as pancreatic islets isolated from nondiabetic mice and human donors exposed to exogenous lysoPIs showed potentiated glucose-stimulated and basal insulin secretion. Finally, addition of exogenous lysoPIs partially rescued impaired glucose-stimulated insulin secretion in islets from mice and humans in the diabetic state. Overall, lysoPIs appear to be lipid species upregulated in the prediabetic stage associated with the loss of β-cells and that support the secretory function of the remaining β-cells. Article Highlights: Circulating lysophosphatidylinositols (lysoPIs) are increased in situations associated with β-cell loss in mice and humans such as (pre-)diabetes, and hemipancreatectomy. Pancreatic islets isolated from nondiabetic mice and human donors, as well as INS-1E β-cells, exposed to exogenous lysoPIs exhibited potentiated glucose-stimulated and basal insulin secretion. Addition of exogenous lysoPIs partially rescued impaired glucose-stimulated insulin secretion in islets from mice and humans in the diabetic state. LysoPIs appear as lipid species being upregulated already in the prediabetic stage associated with the loss of β-cells and supporting the function of the remaining β-cells. (© 2023 by the American Diabetes Association.)
Databáze:	MEDLINE
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