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Oppenländer, L. ; Palit, S. ; Stemmer, K. ; Greisle, T. ; Sterr, M. ; Salinno, C. ; Bastidas-Ponce, A. ; Feuchtinger, A. ; Böttcher, A. ; Ansarullah ; Theis, F.J. ; Lickert, H.

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

Mol. Metab. 54:101330 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
While the effectiveness of bariatric surgery in restoring β-cell function has been described in type-2 diabetes (T2D) patients and animal models for years, the mechanistic underpinnings are largely unknown. The possibility of vertical sleeve gastrectomy (VSG) to rescue a clinically-relevant, late-stage T2D condition 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. Here, 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. 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Beta-cell Dedifferentiation ; Beta-cell Function ; Beta-cell Redifferentiation ; Type-2 Diabetes ; Vertical Sleeve Gastrectomy ; Scrna-sequencing; Beta-cell Dedifferentiation; Intensive Medical Therapy; Gastric Bypass-surgery; Insulin-secretion; Glucose-homeostasis; Placental Lactogens; Bariatric Surgery; Gene-expression; Weight-loss; Islets
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 54, Heft: , Seiten: , Artikelnummer: 101330 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Regeneration Research (IDR)
Institute of Computational Biology (ICB)
Institute of Diabetes and Obesity (IDO)
Research Unit Analytical Pathology (AAP)
Förderungen Helmholtz Foundation
German Center for Diabetes Research (DZD e.V.)