Steele Children's Research Center Exploring Molecular Basis of Atherosclerosis in Diabetes

<p>Atherosclerosis (hardening of the arteries) is the leading cause of premature death ..</p>

Human cells stained for cholesterolAtherosclerosis (hardening of the arteries) is the leading cause of premature death among individuals with type 1 and type 2 diabetes. It is caused by a slow buildup of plaque (an accumulation of fatty substances, cholesterol, calcium and other substances) within the artery wall.

The molecular basis for why individuals with diabetes are more susceptible to atherosclerosis remains unknown.

Grant money from the Father's Day Council Tucson and the National Institutes of Health has enabled Steele Children's Research Center scientist William S. Garver, Ph.D, research associate professor in the department of pediatrics at The University of Arizona College of Medicine, to investigate the molecular basis for why individuals with type 1 and type 2 diabetes develop "diabetic dyslipidemia," characterized by increased triglycerides, increased LDL cholesterol, and decreased HDL cholesterol -- risk factors that contribute to atherosclerosis.

Dr. Garver is researching how glucose and insulin- both altered in individuals with diabetes -affects cholesterol and lipoprotein metabolism. "We know that individuals with diabetes typically have low amounts of 'good' cholesterol - HDL - and high amounts of "bad" cholesterol - LDL," says Dr. Garver. "Since various cells throughout the body are responsible for determining the amount of LDL and HDL cholesterol present in the blood, I suspect that glucose and insulin may affect cellular cholesterol metabolism, and subsequently lipoprotein metabolism."

Using human cells (fibroblasts) grown in culture and exposed to glucose and/or insulin at concentrations that are similar to individuals with diabetes, Dr. Garver monitors the internalization of LDL-derived cholesterol into the cell, the flow of cholesterol throughout different compartments of the cell, and finally the removal of cholesterol by HDL.

His preliminary studies are showing promise. "So far, the results suggest that both glucose and insulin affect important aspects of LDL and HDL metabolism. We have determined which cholesterol transport pathways are regulated by glucose and insulin. The next step is to identify the genes and respective proteins involved in these pathways that are regulated by glucose and insulin," he says. "Knowledge gained from these studies will benefit individuals with type 1 and type 2 diabetes, by providing therapeutic targets for preventing long-term complications like atherosclerosis."