Bariatric surgery induces pancreatic cell transdifferentiation as indicated by single-cell transcriptomics in Zucker diabetic rats.

Autor: Liang Y; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.; Fudan Zhangjiang Institute, Fudan University, Shanghai, China.; Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai, China., Widjaja J; Department of Bariatric and Metabolic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai, China., Sun J; Novogene Bioinformatics Institute, Beijing, China., Li M; Division of Metabolic and Bariatric Surgery, General Surgery Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; National Clinical Research Center for Digestive Diseases, Beijing, China., Qiao Z; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China., Cao T; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China., Wang Y; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China., Zhang X; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China., Zhang Z; Division of Metabolic and Bariatric Surgery, General Surgery Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; National Clinical Research Center for Digestive Diseases, Beijing, China., Gu Y; Department of Bariatric and Metabolic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai, China., Zhang P; Division of Metabolic and Bariatric Surgery, General Surgery Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; National Clinical Research Center for Digestive Diseases, Beijing, China., Yang J; Department of Bariatric and Metabolic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai, China.
Jazyk: angličtina
Zdroj: Journal of diabetes [J Diabetes] 2024 Aug; Vol. 16 (8), pp. e13521. Date of Electronic Publication: 2023 Dec 27.
DOI: 10.1111/1753-0407.13521
Abstrakt: Aims: Bariatric surgery results in rapid recovery of glucose control in subjects with type 2 diabetes mellitus. However, the underlying mechanisms are still largely unknown. The present study aims to clarify how bariatric surgery modifies pancreatic cell subgroup differentiation and transformation in the single-cell RNA level.
Methods: Male, 8-week-old Zucker diabetic fatty (ZDF) rats with obesity and diabetes phenotypes were randomized into sleeve gastrectomy (Sleeve, n = 9), Roux-en-Y gastric bypass (RYGB, n = 9), and Sham (n = 7) groups. Two weeks after surgery, the pancreas specimen was further analyzed using single-cell RNA-sequencing technique.
Results: Two weeks after surgery, compared to the Sham group, the metabolic parameters including fasting plasma glucose, plasma insulin, and oral glucose tolerance test values were dramatically improved after RYGB and Sleeve procedures (p < .05) as predicted. In addition, RYGB and Sleeve groups increased the proportion of pancreatic β cells and reduced the ratio of α cells. Two multiple hormone-expressing cells were identified, the Gcg+/Ppy + and Ins+/Gcg+/Ppy + cells. The pancreatic Ins+/Gcg+/Ppy + cells were defined for the first time, and further investigation indicates similarities with α and β cells, with unique gene expression patterns, which implies that pancreatic cell transdifferentiation occurs following bariatric surgery.
Conclusions: For the first time, using the single-cell transcriptome map of ZDF rats, we reported a comprehensive characterization of the heterogeneity and differentiation of pancreatic endocrinal cells after bariatric surgery, which may contribute to the underlying mechanisms. Further studies will be needed to elucidate these results.
(© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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