Monica Young Choi1, Seong Jun Lim1, Mi Joung Kim1, Yu-Mee Wee1, Hyunwook Kwon1, Chang Hee Jung2, Young Hoon Kim1, Duck Jong Han1, Sung Shin3. 1. Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 2. Asan Diabetes Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 3. Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. sshin@amc.seoul.kr.
Abstract
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, and adipose tissues. METHODS: Eight-week-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 6 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 6 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. 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.
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, and adipose tissues. METHODS: Eight-week-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 6 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 6 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. 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.
Entities:
Keywords:
Insulin sensitivity; Islet transplantation; Streptozotocin; Type 2 diabetes
Authors: Kristine Færch; Dorte Vistisen; Giovanni Pacini; Signe S Torekov; Nanna B Johansen; Daniel R Witte; Anna Jonsson; Oluf Pedersen; Torben Hansen; Torsten Lauritzen; Marit E Jørgensen; Bo Ahrén; Jens Juul Holst Journal: Diabetes Date: 2016-08-08 Impact factor: 9.461