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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)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords 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
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Journal Molecular Metabolism
Quellenangaben Volume: 54, Issue: , Pages: , Article Number: 101330 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Institute of Computational Biology (ICB)
Institute of Diabetes and Obesity (IDO)
CF Pathology & Tissue Analytics (CF-PTA)
POF-Topic(s) 30201 - Metabolic Health
30205 - Bioengineering and Digital Health
90000 - German Center for Diabetes Research
30505 - New Technologies for Biomedical Discoveries
Research field(s) Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP Element(s) G-502300-001
G-503800-001
G-501900-231
G-501900-221
A-630600-001
Grants Helmholtz Foundation
German Center for Diabetes Research (DZD e.V.)
DOI 10.1016/j.molmet.2021.101330
WOS ID WOS:000704168200003
Scopus ID 85115943948
PubMed ID 34500108
Erfassungsdatum 2021-10-13
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