*Purpose: Type 2 diabetes develops in the presence of chronic overnutrition and genetic susceptibility, and causes insulin resistance and relative insulin deficiency. We hypothesized that islet transplantation can improve insulin sensitivity by modifying the mediators of insulin sensitivity in the pancreas, liver, muscle, adipose tissues.

*Methods: Eight-weeks-old male mice were used as both recipients and donors in this study. To induce type 2 diabetes with partial β-cell failure, the mice were fed a high-fat diet for 4 weeks and then injected with low-dose streptozotocin. Approximately 400 islet cells from a donor mouse were injected into the renal capsule of a recipient mouse for islet transplantation. After six weeks following transplantation, the mediators of insulin sensitivity in the pancreas, liver, muscle, and adipose tissues were quantitatively compared between islet-transplanted and non-transplanted groups.

*Results: Intravenous glucose tolerance test showed that whereas the non-transplanted mice failed to show notable reductions in the glucose level, the islet-transplanted mice showed significant reductions in the serum glucose level to ~200 mg/dL at six weeks after islet transplantation. The islet-transplanted mice showed significantly higher Matsuda index and significantly lower HOMA-IR than did the non-transplanted mice, thus signifying improved insulin sensitivity. In the kidney, the insulin/amyloid ratio significantly increased between three and six weeks after islet transplantation. In the liver, the expression levels of insulin sensitivity mediators (ie, adiponectin, GLUT2, IRS-1, and pIRS-1) were significantly higher in the islet-transplanted mice. The islet-transplanted mice also had significantly higher expression levels of IRS-1 in white adipose tissues and GLUT4 in brown adipose tissues compared with non-transplanted mice. Lastly, the islet-transplanted mice showed a significant increase in adiponectin and a decrease in interferon-gamma in white muscle tissues; moreover, the islet-transplanted mice had a significantly higher ratio of phosphorylated AMP-activated protein kinase-α/AMP-activated protein kinase-α in red muscle tissues compared with the non-transplanted mice.

*Conclusions: Islet transplantation resulted in improvements in multiple indices of insulin sensitivity in a murine model of type 2 diabetes. Islet transplantation may be utilized to improve insulin sensitivity in patients with type 2 diabetes.

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