Transforming Growth Factorβ1 Overexpression Is Associated with Insulin Resistance and Rapidly Progressive Kidney Fibrosis under Diabetic Conditions

Diabetes mellitus is a global health problem. Diabetic nephropathy is a common complication of diabetes mellitus and the leading cause of end-stage renal disease. The clinical course, response to therapy, and prognosis of nephropathy are worse in diabetic than in non-diabetic patients. The role of transforming growth factor beta 1 in kidney fibrosis is undebatable. This study assessed whether the overexpression of transforming growth factor beta 1 is associated with insulin resistance and the rapid progression of transforming growth factor beta 1-mediated nephropathy under diabetic conditions. Diabetes mellitus was induced with streptozotocin in wild-type mice and transgenic mice with the kidney-specific overexpression of human transforming growth factor beta 1. Mice treated with saline were the controls. Glucose tolerance and kidney fibrosis were evaluated. The blood glucose levels, the values of the homeostasis model assessment for insulin resistance, and the area of kidney fibrosis were significantly increased, and the renal function was significantly impaired in the diabetic transforming growth factor beta 1 transgenic mice compared to the non-diabetic transgenic mice, diabetic wild-type mice, and non-diabetic mice. Transforming growth factor beta 1 impaired the regulatory effect of insulin on glucose in the hepatocyte and skeletal muscle cell lines. This study shows that transforming growth factor beta 1 overexpression is associated with insulin resistance and rapidly progressive kidney fibrosis under diabetic conditions in mice.

Automated summary

Diabetic nephropathy, a common complication of diabetes mellitus, is the leading cause of end-stage renal disease. The overexpression of transforming growth factor beta 1 is associated with insulin resistance and rapid progression of kidney fibrosis under diabetic conditions.