BBS Faculty Member - Laurie Goodyear

Laurie Goodyear

Department of Medicine

Joslin Diabetes Center
One Joslin Place, Room 520
Boston, MA 02215
Tel: 617-309-2573
Fax: 617-309-2650
Email: laurie.goodyear@joslin.harvard.edu
Visit my lab page here.



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, 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.

Major 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 has turned out to be a master regulator of skeletal muscle metabolism, our group has recently 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. In other work, we are investigating mechanisms through which chronic exercise training improves glucose homeostasis, focusing on adaptations to both muscle and adipose tissue, and the concept of inter-tissue communication.

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 intravital imaging of skeletal muscle of live mice , and methods to identify phosphorylation sites of endogenous skeletal muscle, heart, and adipose tissue proteins using mass spectrometry. 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.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 



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