Introduction and Objective: Recent evidence suggests that extra-pancreatic tissues, including the stomach, may also express insulin. The aim of this study was to investigate whether the human stomach expresses insulin and key β-cell-associated transcriptional markers, and to characterize the cellular and spatial context of such expression.Methods: Gastric biopsies were obtained from 15 human subjects undergoing gastric sleeve or gastric bypass surgery. Insulin (INS) and PDX1 mRNA analysis were performed and samples were processed for histological analysis using immunohistochemistry. Spatial transcriptomic data set from the human stomach were obtained from public available data. Data were processed and normalized scaled with SCTransform() function. Cell types were assigned based on the paired stomach scRNA-seq dataset with provided cell type annotation using Seurat prediction model.Results: Here, we report identification of insulin-positive cells in stomach biopsies obtained from 15 patients undergoing bariatric surgery. Detection of insulin expression varied regionally between corpus (80% of patients), antrum (73%) and the fundus (46%). To assess whether gastric cells transcribe INS, we analyzed spatial transcriptomics data using the NanoStrings Platform and identified INS mRNA positive cells. Similarly, cells positive for the transcription factor PDX1, which controls the expression of INS, were identified in stomach biopsies. Across patient cohorts, gastric INS mRNA levels correlated significantly with the inflammatory marker hsCRP (C-reactive protein).Conclusion: These findings reveal region-specific insulin and PDX1 expression and active INS transcription in the human stomach. These findings raise the possibility that gastric insulin contributes to metabolic regulation, especially in metabolically unhealthy states. The presence of insulin-producing cells suggests a potential endocrine reservoir that could be leveraged for innovative regenerative or reprogramming approaches for treating diabetes.
N.Z. Klöting: None. O. Bondareva: None. S. Krupka: None. B. Sheikh: None. M. Bluher: Consultant; Current; Amgen Inc. Speaker’s Bureau; Current; Abbott. Consultant; Current; Bayer AG, Boehringer Ingelheim International GmbH. Speaker’s Bureau; Current; Daiichi Sankyo. Consultant; Current; Eli Lilly and Company, Novo Nordisk. Speaker’s Bureau; Current; Merck Sharp & Dohme Corp., Sanofi, Novartis AG.
This study was supported by the Deutsche Forschungsgemeinschaft (DFG) project grants (457240345, 511049882), as well as funding from the German Center for Diabetes Research (DZD), free-state of Saxony and Helmholtz Munich.
Source link
Leave a Reply