Adaptive changes of human islets to an obesogenic environment in the mouse

• DOI: 10.1007/s00125-012-2775-y
• Publication Date: 2012-11-29T12:25:40Z
• Authors: S. Gargani; J. Thévenet; J. E. Yuan; B. Lefebvre; N. Delalleau; V. Gmyr; T. Hubert; A. Duhamel; F. Pattou; J. Kerr-Conte
• Keywords: Enteroendocrine cell

In this study, we used an immunodeficient mouse model to explore, in vivo, the longitudinal adaptation of human islets obesogenic environment. Non-diabetic Rag2 –/– mice (n = 61) were transplanted with (400 islet equivalents [IEQ]) from six pancreases: four non-diabetic and two overt metabolic dysfunction (older, high HbAlc or history diabetes). Animals fed for 12 weeks a control high-fat diet (HFD), followed weight, serum triacylglycerol, fasting blood glucose C-peptide. After killed, grafts endogenous pancreas analysed endocrine volume, distribution beta alpha cells, proliferation. Transplanted on HFD gained significantly more weight (p < 0.001) had higher glycaemia (2–12 weeks; p 0.0002) consistently C-peptide levels 0.04) compared those diet. Histology demonstrated doubling graft volume at animals increased cell 0.001), but no change volume. Human function (hyperbolic product HOMA2%BS) was times lower 0.001 vs controls) because insufficient decreased (70%) sensitivity (HOMA%S). obtained donors failed adapt HFD. This study provides direct evidence that both mass, gene expression obesity vivo. The present will facilitate identification mechanisms by which vivo type(s) responsible, factors predisposing cells decompensation.