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

التفاصيل البيبلوغرافية
العنوان: Vertical sleeve gastrectomy triggers fast β-cell recovery upon overt diabetes
المؤلفون: Aimée Bastidas-Ponce, Lena Oppenländer, Anika Böttcher, Ansarullah, Fabian J. Theis, Tobias Greisle, Ciro Salinno, Subarna Palit, Annette Feuchtinger, Heiko Lickert, Kerstin Stemmer, Michael Sterr
المصدر: Molecular Metabolism, Vol 54, Iss, Pp 101330-(2021)
Molecular Metabolism
Mol. Metab. 54:101330 (2021)
بيانات النشر: Elsevier, 2021.
سنة النشر: 2021
مصطلحات موضوعية: Male, Sleeve gastrectomy, Beta-cell dedifferentiation, medicine.medical_treatment, Calorie restriction, Cell, Mice, Obese, Beta-cell function, Mice, Transgenic, Type 2 diabetes, Beta-cell redifferentiation, Bioinformatics, Transcriptome, Mice, Gastrectomy, Insulin-Secreting Cells, Diabetes mellitus, parasitic diseases, medicine, Animals, ddc:610, Molecular Biology, Internal medicine, Beta-cell Dedifferentiation, Beta-cell Function, Beta-cell Redifferentiation, Type-2 Diabetes, Vertical Sleeve Gastrectomy, Scrna-sequencing, Type-2 diabetes, geography, geography.geographical_feature_category, business.industry, Regeneration (biology), Cell Biology, medicine.disease, Islet, RC31-1245, ddc, medicine.anatomical_structure, scRNA-sequencing, Diabetes Mellitus, Type 2, Original Article, Vertical sleeve gastrectomy, business
الوصف: 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.
Highlights • Vertical sleeve gastrectomy (VSG) rapidly improves late-stage diabetes in db/db mice. • VSG recovers β-cell function and induces intrinsic changes in the β-cell transcriptome. • VSG improves markers of β-cell dedifferentiation. • VSG regenerates functional β-cell mass by re-differentiation and proliferation.
وصف الملف: application/pdf
اللغة: English
تدمد: 2212-8778
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::caa18575fb577b45efcc674a3caabd85
http://www.sciencedirect.com/science/article/pii/S2212877821001770
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....caa18575fb577b45efcc674a3caabd85
قاعدة البيانات: OpenAIRE
الوصف
تدمد:22128778