News & Research

    Joslin Diabetes Center, Boston, Massachusetts

Mechanisms of exercise-regulated glucose transport in skeletal muscle

General Research Subject: Type 2 Diabetes

Focus: Exercise\Regulation of Muscle Metabolism

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2008

Project End Date: June 30, 2012

Research Description

Our research is particularly relevant for people with type 2 diabetes, but will also have implications for people with type 1 diabetes. In individuals with diabetes, the skeletal muscles are usually resistant to the actions of insulin, which is a major factor leading to high blood glucose (sugar) levels and poor glucose control. On the other hand, in almost all people with diabetes, their muscles are NOT resistant to the effects of exercise. Thus, the skeletal muscles can take up glucose from the blood in response to exercise, resulting in lower blood glucose levels.

Although it has been known for centuries that exercise can have this beneficial effect in people with diabetes, despite years of investigation it is still not clear how the contracting muscles are able to increase the uptake of glucose into the muscle. During the past years we have begun to understand how exercise 'signals' the muscle to increase glucose transport. A fellow funded by the ADA mentor-based fellowship will determine how these signals lead to the increase in glucose transport in skeletal muscle. This could help in the treatment of diabetes by developing drugs that activate these molecules that signal the increase in glucose transport. In terms of prevention, there is now good evidence that performance of regular physical exercise throughout ones lifetime may delay or prevent the development of type 2 diabetes. The fellow's research projects are also aimed at determining how exercise is able to have these preventative effects.

Reseacher Profile

Mentor: Laurie J. Goodyear, PhD   Postdoctoral Fellow: Taro Toyoda, MS, PhD

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

Regular exercise is recommended for people with diabetes. It helps the skeletal muscles to be more sensitive to the actions of insulin and therefore lowers blood glucose levels and reduces the dose of exogenous insulin required for adequate glucose control. Likewise, exercise has been shown to prevent or delay the development of type 2 diabetes. My area of research focuses in elucidating the molecular mechanisms through which exercise promotes these beneficial effects in people with diabetes. Specifically, I am studying the potential role that the signaling molecules activated by muscle contraction could play in mediating the effects of exercise in muscle glucose metabolism. With support from the ADA, we have made significant progress during the last several years in defining this complex mechanism. Understanding how exercise functions to regulate glucose metabolism could lead to new approaches for the prevention and treatment of diabetes.

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

I am interested in elucidating the molecular mechanisms involved in regulating the effects of exercise on carbohydrate and fat metabolism in people with diabetes. Clarifying these mechanisms could lead to new strategies that are beneficial for the prevention and treatment of type 2 diabetes. For example, we know that insulin-independent signaling molecules are involved in stimulating glucose uptake into the contracting muscles during exercise. Since not all the people with diabetes are capable of exercising, designing a medication that would activate these molecules and therefore 'mimic' the effects of exercise could prove useful in decreasing blood glucose levels. Our work will also help understand the types of exercise that will activate the critical molecules that lead to an increase in glucose uptake and the subsequent glucose lowering effects of exercise.

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

The major goal of my research has always been to try to understand how exercise is able to have beneficial effects in people with Diabetes. This work is becoming even more important with the increase in obesity and diabetes, and the decrease in the typical American's level of activity. A specific question we are addressing is how does exercise so dramatically lower blood glucose levels when people are still resistant to insulin? This award will allow my laboratory to test what I believe to be the most exciting hypothesis in this area of research in many years. Funding for a post doctoral fellow from the ADA will allow us to carry out critical studies that will help elucidate the basic molecular mechanisms underlying the beneficial effects of exercise.

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

In my view, the most important aspects of future diabetes research are: 1) Designing modalities to prevent diabetes and its complications. 2) Creating new strategies, including pharmacological interventions, in order to preserve -cell function and to make tissues more sensitive to insulin. 3) Designing glucose monitoring devices and insulin delivery systems that are more practical for people with diabetes.