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

Mol. Metab. 54:101330 (2021)
Verlagsversion DOI
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
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
Begutachtungsstatus Peer reviewed
Förderungen Helmholtz Foundation
German Center for Diabetes Research (DZD e.V.)