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Restaurer la fonction bêta pancréatique de la souris leptine déficiente par la chirurgie bariatrique

Abstract : EGA (entero-gastro-anastomosis) is a gastric bypass procedure adapted to rodent. EGA in leptin deficient ob/ob mice improves glucose tolerance by increasing pancreatic insulin content and glucose stimulated insulin secretion in vivo without persistent body weight loss dietary restriction, modification of body composition / energy expenditure. We do not observe differences in islets ‘number or size after EGA. Insulin gene expression, beta-cell proliferation (Ki67 index) and insular immune infiltration are also unchanged. Transcriptomic analysis of pancreatic islets showed that bariatric surgery differentially regulated 193 genes and 27 miRs. Interestingly, the surgery normalized molecular defects (down regulation of TRPM5, GLUT2, GCK, connexin 36) and functional alteration (high sensitivity of islets to low glucose levels) observed in diabetic ob pancreatic islets. In addition, the surgery promoted the enrichment of 227 biological process, composed of genes with known or undetermined beta cell function, especially 21 genes are involved in the hormone transport and 20 genes in the hormone secretion biological process. Computational analysis predicted that 7 of 27 miRs (324-3p, 380-3p, 671-5p, 1927, 6904-5p, 6918-5p and 7682-3p) are hubs in the miRs-gene interaction network. Altogether, our data highlighted novel molecular mechanisms in the resolution of diabetes after bariatric surgery. Overall, diabetes resolution in our model appears to be totally independent of body weight.
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Chloé Amouyal. Restaurer la fonction bêta pancréatique de la souris leptine déficiente par la chirurgie bariatrique. Endocrinologie et métabolisme. Sorbonne Université, 2019. Français. ⟨NNT : 2019SORUS010⟩. ⟨tel-02935890⟩

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