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

• Published in: Diabetologia 2013-02, Vol.56 (2), p.350-358
• Main Authors: Gargani, S., Thévenet, J., Yuan, J. E., Lefebvre, B., Delalleau, N., Gmyr, V., Hubert, T., Duhamel, A., Pattou, F., Kerr-Conte, J.
• Format: Article
• Language: English
• Subjects: Adaptation; Animals; Biological and medical sciences; Diabetes; Diabetes. Impaired glucose tolerance; Diet; Diet, High-Fat - adverse effects; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gene expression; Glucose; Histology; Human Physiology; Humans; Immunohistochemistry; Insulin resistance; Insulin-Secreting Cells - metabolism; Internal Medicine; Islets of Langerhans - metabolism; Islets of Langerhans - physiology; Islets of Langerhans Transplantation; Longitudinal studies; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Mice; Obesity; Obesity - metabolism; Peptides; Polymerase Chain Reaction
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-012-2775-y

Aims/hypothesis In this study, we used an immunodeficient mouse model to explore, in vivo, the longitudinal adaptation of human islets to an obesogenic environment. Methods Non-diabetic Rag2 –/– mice ( n  = 61) were transplanted with human islets (400 islet equivalents [IEQ]) from six pancreases: four non-diabetic and two with overt metabolic dysfunction (older, high HbA lc or history of diabetes). Animals were fed for 12 weeks with a control or high-fat diet (HFD), and followed for weight, serum triacylglycerol, fasting blood glucose and human C-peptide. After the mice were killed, human grafts and the endogenous pancreas were analysed for endocrine volume, distribution of beta and alpha cells, and proliferation. Results Transplanted mice on an HFD gained significantly more weight ( p