News & Research

    Joslin Diabetes Center, Boston, Massachusetts

Mechanisms regulating exercise-induced improvements in glucose homeostasis

General Research Subject: Type 2 Diabetes

Focus: Adipocytes, Exercise, Exercise\Regulation of Muscle Metabolism, Integrated Physiology, Integrated Physiology\Muscle

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2012

Project End Date: June 30, 2016

Research Description

Research in the Goodyear laboratory is particularly relevant for people with type 2 diabetes, but also has 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 solid evidence that performance of regular physical exercise throughout one's 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.

Research Profile

Mentor: Laurie J. Goodyear, PhD
Postdoctoral Fellow: Xu Yan, PhD

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

Research in my laboratory is particularly relevant for people with type 2 diabetes, but also has implications for people with type 1 diabetes. In individuals with diabetes, the skeletal muscles are usually resistant to the actions of insulin, 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. A single bout of exercise increases glucose transport in skeletal muscle, and consistent exercise training from repeated bouts of exercise over weeks, months, or years has beneficial effects on whole body and tissue glucose homeostasis in people with diabetes. Despite the importance of exercise for the prevention and treatment of diabetes, the molecular mechanisms underlying these adaptations are not well understood.

A fellow funded by this ADA mentor-based fellowship will study the role of specific proteins and tissues that we believe play an important role in signaling glucose transport in skeletal muscle. The information discovered in these studies could help in the treatment of diabetes by initiating the development of drugs to activate these molecules, thereby creating an automatic signal to increase glucose transport. In terms of prevention, there is now solid evidence that routine physical exercise throughout one’s 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.

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

My laboratory aims to elucidate the molecular mechanisms involved in regulating the beneficial effects of exercise on glucose transport and metabolism in people with diabetes. Clarifying these clinically important mechanisms could lead to new strategies that are beneficial for preventing and treating type 2 diabetes, as well as improving carbohydrate metabolism and averting long-term consequences in people with both type 1 and 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 people with diabetes are capable of exercising, designing a medication to activate these molecules and therefore mimic the effects of exercise could prove effective in decreasing blood glucose levels. Our work will also help to 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 understand how exercise is able to have numerous beneficial effects in people with diabetes. This work becomes increasingly more important with the rise of obesity and diabetes, and the decrease in the typical American's level of activity. A specific question my laboratory is addressing is how exercise so dramatically lowers blood glucose levels in people with diabetes when they are still resistant to insulin. This award will allow my laboratory to test several exciting hypotheses in this area of research. 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, to preserve beta-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.