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Laurie J. Goodyear, Ph.D.

Research Summary

The Effects of Exercise

It is well established that the performance of regular physical exercise results in numerous health benefits, including a reduced risk of developing type 2 diabetes.  Physical exercise is also widely accepted as a clinically important modality to decrease blood glucose concentrations in patients with diabetes.  Even a single session of exercise can lower blood glucose concentrations by stimulating glucose uptake into the muscles and making the muscles more sensitive to the effects of insulin.  Regular physical exercise also has many additional health benefits important to people with diabetes including lowering blood pressure, improving lipid levels and lowering the risk of heart disease.  Despite the profound clinical importance of the metabolic effects of exercise, until recently, there has been little focus on the underlying molecular mechanisms that mediate these responses.

Research in the Goodyear laboratory is focused on understanding the molecular mechanism by which physical exercise exerts beneficial effects on health.  The rationale for this work stems from the well-established findings that the performance of regular physical exercise results in numerous health benefits, including a reduced risk of developing type 2 diabetes.  Physical exercise is also widely accepted as a clinically important modality to decrease blood glucose concentrations in patients with diabetes, due largely to an increase in the rate of glucose transport into the contracting skeletal muscles and an increase in insulin sensitivity in the period following exercise.  Despite the profound clinical importance of the metabolic effects of exercise, until recently, there has been little focus on the underlying molecular mechanisms that mediate these responses.

Specific goals of the work in the Goodyear laboratory include elucidating the mechanisms through which a single bout of physical exercise increases glucose transport in skeletal muscle and determining the mechanisms through which chronic exercise training improves overall metabolic homeostasis.  Our work has shown that muscle contractile activity increases glucose transport in muscle through intracellular signal transduction mechanisms that are distinct from that of insulin.  The putative signals have long been elusive, but in recent years we have identified the AMP-activated protein kinase (AMPK) as a mediator of insulin-independent glucose transport in skeletal muscle.  These studies have contributed to worldwide interest in AMPK as a master regulator of metabolic and transcriptional functions in tissues and cells throughout the body.  Furthermore, this work has led to intensive work in the pharmaceutical industry focused on the development of an AMPK activator as a novel drug target for the treatment of diabetes.

Although AMPK is a master regulator of skeletal muscle metabolism, our group has determined that AMPK is not necessary for many of the effects of exercise on skeletal muscle metabolism, including contraction-stimulated glucose transport.  We have discovered that there are additional signaling systems that mediate the beneficial effects of exercise in skeletal muscle, and we are intensively studying these molecules.  For example, we have determined that sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle, and are currently investigating several other AMPK-related kinases.  In other studies of glucose transport regulation we have developed a novel imaging system to elucidate the kinetics of contraction-induced GLUT4 translocation in skeletal muscle, and discovered that Myo1c, a protein implicated in GLUT4 translocation in adipocytes, is a novel mediator of insulin- and contraction-stimulated glucose uptake in skeletal muscle.  In addition, we have published very novel data on the role of TC1D1, TC1D4, and CaMKII in the regulation of skeletal muscle metabolism.

Our laboratory has been at the forefront of research in skeletal muscle metabolism through the use of a combination of molecular and physiological approaches including contraction of rodent skeletal muscles in vitro and in situ, wheel cage training of animals, knockout and transgenic mice, overexpressing foreign proteins into adult rodent skeletal muscle using electroporation, whole body metabolic assessments, and methods to identify phosphorylation sites of endogenous skeletal muscle proteins using mass spectrometry.

In addition to studies focused on skeletal muscle, more recently, our laboratory has investigated adipose tissue function using a transplantation model.  For one project, we have studied brown adipose tissue’s function in energy expenditure and the effect of its transplantation on metabolism.  In other work, we are investigating mechanisms through which chronic exercise training improves glucose homeostasis, focusing on the novel hypothesis that adaptations to adipose tissue improves glucose tolerance and insulin sensitivity.  This ongoing work has identified numerous novel secreted proteins in adipose tissue which we are studying for putative effects on metabolism.  All of these investigations should help define the molecular basis for the important adaptations that occur with exercise, and will have important ramifications for patients with metabolic and cardiovascular diseases.

General Projects

- Regulation of glucose transport in skeletal muscle
- Molecular signaling mechanisms regulating contraction-stimulated glucose metabolism in skeletal muscle
- The role of AMPK and AMPK-related kinases in skeletal muscle, heart and adipose tissue metabolism
- Mechanisms regulating the beneficial effects of exercise to improve whole body glucose homeostasis in people with diabetes

Biography

Laurie J. Goodyear is a Senior Investigator and Head of the Section on Integrative Physiology and Metabolism at the Joslin Diabetes Center and an Associate Professor in Medicine at Harvard Medical School. She is a graduate of Springfield College and the University of South Carolina, and obtained her Ph.D. degree in Cell Biology from the University of Vermont. She completed her postdoctoral research at Joslin in the lab of Dr. Robert J. Smith of the Metabolism Section. Dr. Goodyear has been the recipient of several awards including Career Development Awards from the American Diabetes Association and Juvenile Diabetes Foundation, a New Investigator Award from the American College of Sports Medicine, and the 2012 Edward F. Adolph Distinguished Lectureship of the American Physiological Society. She has served as Deputy Chair for the Biochemical Journal and an Associate Editor for Diabetes, and has served on several grant review committees for the National Institutes of Health. She has had the honor of giving over 75 invited lectures at national and international conferences.

Page last updated: April 23, 2014