News & Research

    University of Illinois at Chicago, Chicago, Illinois

13C NMR studies of lipoprotein metabolism in diabetes cardiomyopathy

General Research Subject: Type 2 Diabetes

Focus: Diabetic Dyslipidemia, Integrated Physiology\Fatty Acid Metabolism, Integrated Physiology\Muscle

Type of Grant: Basic Science

Project Start Date: January 1, 2012

Project End Date: December 31, 2014

Diabetes Type: Type 2 diabetes

Partial Funding by the FM Kirby Foundation

Research Description

Diabetes cardiomyopathy is a clinical myocardial condition characterized by heart dysfunction. It is the major cause of death in diabetes, and accounts for some 50% of all fatalities. In diabetes, the uptake of glucose into the cells of the heart is reduced, while fat uptake increases significantly and accumulates in the cells as large droplets. Too much fat results in both high levels of toxic molecules and a loss in force production. The knowledge of why fats accumulate in the heart may provide insight into novel therapies for treatment of heart disease in diabetes. Fats circulate in our blood as fat molecules attached to albumin or as fat molecules stored within lipid particles called lipoproteins. Earlier studies examined the use of the fat molecules attached to albumin, even though the fat from the lipoproteins might be the major source of fuel in heart. Few studies have examined lipoprotein utilization in heart because it has been difficult to make or buy the lipoproteins for experiments. In this study, a new method will be used to make lipoproteins for heart studies. The goal of the study is to determine if the fat and glycerol from the lipoproteins are used by the heart in diabetes differently from the fat molecules attached to albumin. The current study suggests gene therapy strategies that limit the entry of fats into the cells of the heart may restore the ability of the heart to pump blood.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

Diabetes cardiomyopathy is a clinical myocardial condition characterized by heart dysfunction. It is the major cause of death in diabetes, and accounts for some 50% of all fatalities. In diabetes, fat uptake into the heart increases significantly, and it accumulates in the cells as large droplets. Too much fat results in both high levels of toxic molecules and a loss in force production. The knowledge of why fats accumulate in the heart may provide insight into novel therapies for treatment of heart disease in diabetes. Fats circulate in our blood as fat molecules attached to albumin or as fat molecules stored within lipid particles called lipoproteins. Most studies have examined heart uptake of the fat molecules attached to albumin, even though the fat from the lipoproteins might be the major source of fuel in heart. Few studies have examined lipoprotein utilization in heart because it has been difficult to make or buy the lipoproteins for experimental measurements. In this study, a new method will be used to make lipoproteins for NMR studies of heart metabolism. The goal of the study is to determine if the fat and glycerol from the lipoproteins are metabolized by the heart differently with diabetes. The current study will examine a gene therapy strategy that limits the entry of fats into the cells of the heart. We will determine if this strategy improves the ability of the heart to pump blood.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

This project seeks to discover previously unknown mechanisms linked to heart disease and type-2 diabetes. We are particularly focused on changes in the metabolic activity of the heart. Specifically, if we can understand the role that fats play in the development of this heart disease, we may eventually be able to interrupt the disease process and prolong healthy life. It may also lead to new ways to identify people at the highest risk of developing these problems, and thereby provide direction toward the development of new preventive treatments. This project will also test a new gene therapy treatment for the heart in diabetics. The heart has been a particularly difficult organ to treat by gene therapy strategies, because it is constantly moving / beating. Just as quickly as we deliver genes to the heart, they are pumped out and come to rest in the liver. We have advanced a gene delivery technique to the heart that provides a high level of gene transfer to the heart without gene transfer to other organs. We will use this approach to determine if a gene therapy strategy designed to reduce the uptake of fat into the heart leads to improved heart metabolism and function.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

In the United States 26 million adults and children have diabetes. The prevalence of this disease is expected to nearly double by the year 2020. Indeed, each of us has a close friend or family member challenged by this illness. While the scientific advances of the recent decades have significantly improved the longevity of their lives, the quality of their life is often compromised. My goal is to add to the basic scientific understanding of the disease, which would lead to treatment strategies designed to improve the quality of life. Scientifically, this research project seeks to advance a new technique for studying cardiac lipoprotein metabolism at a level that otherwise has not been available. With the development of any new technology, new and often unexpected findings provide novel insight into the underlying maladaptive processes of the disease. This grant enables the development of this novel method of detection, with the data serving as the basis of future and more focused mechanistic studies from my laboratory.

In what direction do you see the future of diabetes research going?

Physical inactivity, obesity, and diet are often blamed for the rising incidence of diabetes worldwide. However, we are also living longer as new plague fighting drugs and chemo/radiation therapies reduce the incidence of death by stroke, heart attack, and cancer. Our survival exposes a number of secondary underlying diseases, including diabetes. While diet and exercise will help reduce the onset and severity of this disease, it is not the cure. More effective prevention strategies, more effective drugs to control fat and glucose metabolism, insulin resistance, and beta cell function, and effective strategies to lower cardiovascular risk remains key.