News & Research

    University of North Carolina Chapel Hill, Chapel Hill, North Carolina

Insulin is a primary mediator between the positive energy imbalance and development of type 2 diabetes

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Insulin Action\Insulin Resistance, Insulin Action\Metabolism, Insulin Action\Signal Transduction

Type of Grant: Basic Science

Project Start Date: July 1, 2009

Project End Date: June 30, 2013

Research Description

Insulin resistance and its numerous associated diseases such as Type 2 diabetes (T2DM), heart attacks, strokes, Alzheimer's disease, asthma, cancers, and aging are a major health problem in industrialized countries. Insulin resistance is closely associated with the positive energy imbalance due to over eating and/or immobility. However, the primary link between the positive energy imbalance and insulin resistance is still unknown. Our long-term goal is to find this primary player and ultimately provide new targets for prevention and treatment of insulin resistance and its associated diseases. Our preliminary studies imply that insulin itself is the primary player. Insulin is released to the blood whenever nutrients are absorbed into the blood.

The blood insulin returns to a low basal level when all nutrients have left the blood. Thus, insulin normally does not cause any trouble. However, the excess nutrients may keep nutrients in the blood for a longer time, resulting in a simultaneous increase in the blood insulin level. Insulin then spend a longer time in driving the nutrients away from the blood to be stored as fat in the fat tissue at beginning, and later in non-fat tissues, and consequently causes insulin resistance. In this study, we will test the main hypothesis that insulin is the primary mediator in the development of insulin resistance and T2DM. 

Completion of this study may provide new understanding of insulin resistance and T2DM and new targets for prevention and treatment of insulin resistance and other metabolic disorders such as T2DM.

Reseacher Profile

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

We investigate the role of insulin in the production of new mitochondria via biogenesis and autophagy-dependent removal of aged/dysfunctional mitochondria. Both production of new mitochondria and removal of aged/dysfunctional mitochondria are important for maintaining the normal mitochondrial function. Mitochondrial dysfunction is closely linked to oxidative stress and insulin resistance. Insulin resistance is either a precursor or a key component of numerous major diseases primarily caused by the modern lifestyle that is featured by overeating and physical inactivity.

These diseases include obesity, metabolic syndrome, cardiovascular disorders (CVD, including strokes), Alzheimer's disease, depression, asthma, cancers, and aging, etc. We have recently observed that prolonged exposure to insulin, which can be caused by overeating and/or physical activity, suppresses both mitochondrial biogenesis and autophagy in the presence of insulin resistance/hyperinsulinemia. We are currently investigating the associated mechanisms. This part of the work is currently supported by the American Diabetes Association (ADA).   

Results from this projects may provide totally new idea and approach for prevention and treatment of insulin resistance and its many associated modern diseases obesity, metabolic syndrome, cardiovascular disorders (CVD, including strokes), Alzheimer's disease, depression, asthma, cancers, and aging, etc.

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

I will explain to the patient how diabetes is caused by the modern lifestyle that is featured by overeating and physical inactivity. Specifically, I will tell the patient how overeating and physical inactivity affect mitochondrial function and lead to mitochondrion-derived oxidative stress and insulin resistance. Diabetes is only a small part of insulin resistance. Insulin resistance leads to not only diabetes, but also cause cardiovascular disorders, Alzheimer's disease (including strokes), depression, cancers, and aging, etc. Thus, the key to prevent and treat diabetes is to restore mitochondrial function by eating less and increasing physical activity. Medicines can help minimize but do not solve the problem.  

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

Previously as a clinician, I had first-hand experience with many patients with diabetes and other diseases associated with insulin resistance such as cardiovascular disorders, depression, Alzheimer's disease, cancers, aging, etc. I knew that these diseases are primarily caused by the modern 'rich' life, but did not know how the 'positive energy imbalance' is converted into insulin resistance and numerous associated diseases such as diabetes. Insulin resistance is basically associated with everyone's directly or indirectly. That was why I became involved in the research of diabetes.

This award will provide me a powerful toll for pursuing my research interest in diabetes. Specifically, this award will help my find the clue how the 'powerhouse' of a cell, mitochondria, is overwhelmed by the excess nutrients and lack of physical activity, pave the way for more federal funding to studying the mechanism of insulin resistance and diabetes.

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

I see more focus on studying the dynamic course about how the positive energy imbalance is gradually converted into ectopic fat oxidation, oxidative stress, insulin resistance/hyperinsulinemia (excess exposure to insulin) and later to insulin deficiency-associated diseases such as diabetes and cardiovascular events (myocardiac infarction, strokes, and embolisms of limp arteries). Understanding the dynamic course of insulin resistance and diabetes will help finding ways to early prevent the development of insulin resistance and diabetes, and reverse insulin resistance and associated diseases including diabetes and atherosclerosis.