Islet isograft transplantation improves insulin sensitivity in type 2 diabetes mice induced by high fat diet combined with low-dose streptozotocin
Seong Jun Lim1, Youngmin Ko1, Monica Young Choi1, Hey Rim Jung1, Mi Joung Kim1, Yu-Mee Wee1, Hyunwook Kwon1, Dong Hyun Kim1, Joo Hee Jung1, Young Hoon Kim1, Duck Jong Han1, Sung Shin1.
1Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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.
This research was performed with grants support from the Asan Institute for Life Sciences..
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