Please use this identifier to cite or link to this item:
|Title:||Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice.|
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 2
Green Fluorescent Proteins
|Citation:||Dis Model Mech.2016 11;(9)11:1271-1281|
|Abstract:||Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte--specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8 weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus.|
|Appears in Collections:||Hospitales > H. U. Santa Cristina > Artículos|
Files in This Item:
The file with the full text of this item is not available due to copyright restrictions or because there is no digital version. Authors can contact the head of the repository of their center to incorporate the corresponding file.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.