JDRF Funded Research : Juvenile Diabetes Research Foundation International
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JDRF Funded Research

JDRF-Funded Research:  Lay Abstract

Name:   William Durante ,Ph.D.
Baylor College of Medicine, USA
Lab Website:  

Project duration:   01-MAY-2004   to   30-APR-2007
Priority Research Grant

Project grant award:   $495,000.00*

* Total Grant award amount may vary depending on budget adjustments and it is contingent upon research progress and availability of JDRF research funds. 		File No:   1-2004-233

(Abstract Dt: 30-APR-2007)

Therapeutic Area:   Complications Therapies

Grant Status: Inactive
Project Title
Arginase and Vascular Remodeling in Diabetes
Objective
The studies outlined in this proposal will investigate the metabolism of the amino acid L-arginine by vascular cells in diabetes. We propose that an alteration in the metabolism of L-arginine by a protein known as arginase I contribute to the development of blood vessel disease in type I diabetes.
Background/Rationale
Type I diabetes is associated with blood vessel disease, leading to increased risk of heart attack, stroke, and limb amputations. Blood vessel disease in diabetes is characterized by overactivity of specific cells in blood vessels known as vascular smooth muscle cells. The abnormal activation of these cells leads to excessive cell growth, migration, and collagen secretion resulting in the narrowing and eventual blockage of blood vessels. Recently, we discovered that the protein arginase I plays a role in elevating aspects of smooth muscle cell activity to dangerously high levels. Interestingly, in preliminary studies, we found that smooth muscle cells exposed to high sugar levels demonstrate an alteration in L-arginine metabolism that is associated with elevated arginase I activity. We also discovered that damaged blood vessels have increased levels of arginase I.
Description of Project
Initial experiments will examine the effect of high sugar levels on the activity and levels of arginase I in vascular cells. These studies will also investigate whether the exposure of cells to high levels of sugar promotes the metabolism of L-arginine to polyamines and L-proline which are required for cell growth and collagen synthesis. We will also determine if blocking arginase I activity with drugs or molecular techniques can prevent the excessive growth, migration, and collagen synthesis of smooth muscle cells exposed to high concentrations of glucose. Finally, we will determine whether inhibition of arginase I by drugs or molecular techniques can prevent the extreme narrowing of arteries that is observed in diabetic animals following damage to blood vessels.
Anticipated Outcome
The experiments described in this proposal will determine the regulation and role of that arginase I plays in promoting the development of vascular disease in type I diabetes.
Relevance to Type I Diabetes
The experiments described in this proposal will determine the regulation and role of that arginase I plays in promoting the development of vascular disease in type I diabetes.