Vertical sleeve gastrectomy triggers fast β-cell recovery upon overt diabetes.

Autor:	Oppenländer L; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, 85764, Neuherberg, Germany; Technical University of Munich, School of Medicine, 81675, Munich, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany., Palit S; Institute of Computational Biology, Helmholtz Center Munich, 85764, Neuherberg, Germany; Technical University of Munich, TUM School of Life Sciences Weihenstephan, 85354, Freising, Germany., Stemmer K; Institute of Diabetes and Obesity, Helmholtz Center Munich, 85764, Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany; Rudolf Buchheim Institute of Pharmacology, Justus Liebig University, 35392, Giessen, Germany., Greisle T; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, 85764, Neuherberg, Germany; Technical University of Munich, School of Medicine, 81675, Munich, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany., Sterr M; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, 85764, Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany., Salinno C; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, 85764, Neuherberg, Germany; Technical University of Munich, School of Medicine, 81675, Munich, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany., Bastidas-Ponce A; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, 85764, Neuherberg, Germany; Technical University of Munich, School of Medicine, 81675, Munich, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany., Feuchtinger A; Core Facility Pathology and Tissue Analytics, Helmholtz Center Munich, 85764, Neuherberg, Germany., Böttcher A; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, 85764, Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany., Ansarullah; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, 85764, Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany. Electronic address: ansar.aman@jax.org., Theis FJ; Institute of Computational Biology, Helmholtz Center Munich, 85764, Neuherberg, Germany; Department of Mathematics, Technical University of Munich, 85748, Garching, Germany; Technical University of Munich, TUM School of Life Sciences Weihenstephan, 85354, Freising, Germany. Electronic address: fabian.theis@helmoltz-muenchen.de., Lickert H; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, 85764, Neuherberg, Germany; Technical University of Munich, School of Medicine, 81675, Munich, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany; Department of Medicine, Technical University of Munich, 81675, Munich, Germany. Electronic address: heiko.lickert@helmholtz-muenchen.de.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2021 Dec; Vol. 54, pp. 101330. Date of Electronic Publication: 2021 Sep 06.
DOI:	10.1016/j.molmet.2021.101330
Abstrakt:	Objective: The effectiveness of bariatric surgery in restoring β-cell function has been described in type-2 diabetes (T2D) patients and animal models for years, whereas the mechanistic underpinnings are largely unknown. The possibility of vertical sleeve gastrectomy (VSG) to rescue far-progressed, clinically-relevant T2D and to promote β-cell recovery has not been investigated on a single-cell level. Nevertheless, characterization of the heterogeneity and functional states of β-cells after VSG is a fundamental step to understand mechanisms of glycaemic recovery and to ultimately develop alternative, less-invasive therapies. Methods: We performed VSG in late-stage diabetic db/db mice and analyzed the islet transcriptome using single-cell RNA sequencing (scRNA-seq). Immunohistochemical analyses and quantification of β-cell area and proliferation complement our findings from scRNA-seq. Results: We report that VSG was superior to calorie restriction in late-stage T2D and rapidly restored normoglycaemia in morbidly obese and overt diabetic db/db mice. Single-cell profiling of islets of Langerhans showed that VSG induced distinct, intrinsic changes in the β-cell transcriptome, but not in that of α-, δ-, and PP-cells. VSG triggered fast β-cell redifferentiation and functional improvement within only two weeks of intervention, which is not seen upon calorie restriction. Furthermore, VSG expanded β-cell area by means of redifferentiation and by creating a proliferation competent β-cell state. Conclusion: Collectively, our study reveals the superiority of VSG in the remission of far-progressed T2D and presents paths of β-cell regeneration and molecular pathways underlying the glycaemic benefits of VSG. (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu