Exendin-4 Treatment Improves Metabolic Control After Rat Islet Transplantation to Athymic Mice with Streptozotocin-induced Diabetes.
From: CLINTEC, Division of Transplantation Surgery, Karolinska Institutet, Stockholm, Sweden.
Diabetologia
- Publish Date: Jun 2006
- ISSN: 0012-186X
- Volume: 49
- Issue: 6
- Pages: 1247-53
- Medium: Print
- Language: English
- Citation (JAMA): Sharma A, Sörenby A, Wernerson A, et al. Exendin-4 Treatment Improves Metabolic Control After Rat Islet Transplantation to Athymic Mice with Streptozotocin-induced Diabetes.. Diabetologia Jun 2006;49:1247-53
Abstract
AIMS/HYPOTHESIS: Early islet graft survival is crucial in determining the outcome after clinical islet transplantation. Exendin-4 has anti-apoptotic and beta cell proliferative properties, which could improve islet graft survival and function. The aim of these studies was to evaluate the effect of exendin-4 on graft function after islet transplantation. MATERIALS AND METHODS: Rat islets were transplanted under the kidney capsule of diabetic athymic mice. First, we performed a dose-finding study and found that 30 islets just failed to cure diabetic mice. In the following two studies, we transplanted 30 islets and treated the mice that had received these islets with exendin-4 i.p. (100 ng/mouse) once daily for 1 week. Blood glucose levels and body weights were used as evaluation criteria. In the short-term study evaluation was done at day 8. This study was followed by a long-term study that was evaluated at 4 weeks. In this study, islets were precultured with exendin-4 (0.1 nmol/l) in addition to the treatment given to mouse-recipients of transplanted islets. The cured mice underwent an intraperitoneal glucose tolerance test (IPGTT). RESULTS: In the short-term study, 63% of exendin-4-treated mice achieved graft function compared with 21% of untreated mice (p = 0.033). In the long-term study, 88% of treated mice had functioning grafts compared with 22% of controls (p = 0.015). Cured mice showed a normal response in the IPGTT, comparable to that of healthy mice. Exendin-4-treated mice gained significantly more weight than their untreated counterparts. CONCLUSIONS/INTERPRETATION: Islet preculture and a short course of therapy with exendin-4 improves metabolic control after rat islet transplantation in athymic mice. The beneficial effect lasts beyond the treatment period.
Mesh Headings (Keywords): Animals, Blood Glucose, Diabetes Mellitus, Experimental, Glucose Tolerance Test, Graft Survival, Islets of Langerhans Transplantation, Male, Mice, Mice, Nude, Peptides, Rats, Rats, Sprague-Dawley, Transplantation, Heterologous, Venoms
Check for Full Text / PubMed Unique Identifier (PMID): 16609877
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.