Type 2 diabetes (T2DM) is often associated with obesity and develops when chronic overnutrition coexists with genetic susceptibility to cause impaired insulin signaling, also known as insulin resistance, as well as a relative insulin deficiency. We hypothesized that islet transplantation can improve insulin sensitivity by modifying insulin sensitivity mediators in pancreas, liver, muscle, fat tissues. Eight-week-old male mice (C57BL/6N) were used as both recipients and donors in this study. After 4 weeks high fat diet (HFD), low dose streptozotocin (STZ) (40mg/kg, intraperitoneal, twice within 24 hours) was administered to induce T2DM with partial beta cell failure. About 400 islet cells from a donor were injected in the capsule of a kidney of a recipient for islet transplantation (ITx). After six weeks post-transplant, mediators of insulin sensitivity in pancreas, liver, muscle, and fat tissues were quantitatively compared between HFD/STZ and HFD/STZ/ITx. Intravenous glucose tolerance test showed that the glucose level returned to less than 200 mg/dL in the HFD/STZ/ITx group whereas failed in the HFD/STZ group. In pancreas, insulin/glucagon ratio, insulin/amyloid ratio, and relative intensity of pIRS-1 were significantly increased in the HFD/STZ/ITx mice compared with HFD/STZ. In liver, relative intensities of adiponectin, GLUT2, IRS-1, and pIRS-1 were significantly increased in the HFD/STZ/ITx mice. In white fat tissues, the intensity of IRS-1 were higher in the HFD/STZ/ITx mice. In white muscle tissues, there was a significant increase of adiponectin and decrease of interferon gamma in the HFD/STZ/ITx mice. In red muscle tissues, meanwhile, there was an significant increase of the ratio of pAMPKa/AMPKa in the HFD/STZ/ITx mice compared with HFD/STZ.
In conclusion, we demonstrated that islet transplantation increase mediators which enhance insulin sensitivity in several organs in HFD/STZ induced T2DM mouse model.