Mechanisms by Which Strength Training Ameliorates the Metabolic Syndrome
| Status: | Completed |
|---|---|
| Conditions: | Endocrine, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 2/8/2015 |
| Start Date: | January 2008 |
| End Date: | June 2013 |
| Contact: | Charles A Stuart, MD |
| Email: | stuartc@etsu.edu |
| Phone: | 423-439-6282 |
Prevention and treatment strategies for diabetes use exercise as the cornerstone. Even
though endurance training and strength training both improve insulin resistance, strength
training may be better suited for persons at risk for type 2 diabetes. We will expand our
pilot studies of muscle adaptation induced by resistance exercise training to determine the
biochemical mechanisms that will cause people with the Metabolic Syndrome to secure major
benefit from intense strength training.
though endurance training and strength training both improve insulin resistance, strength
training may be better suited for persons at risk for type 2 diabetes. We will expand our
pilot studies of muscle adaptation induced by resistance exercise training to determine the
biochemical mechanisms that will cause people with the Metabolic Syndrome to secure major
benefit from intense strength training.
Life style alterations can be powerful deterrents to developing type 2 diabetes and are
cornerstones of the treatment of this condition. Both aerobic and resistance exercise
improve diabetes blood glucose control and insulin resistance. These two types of exercise
appear to exert their effects on different muscle fiber types - red for endurance and white
for strength. Similar to the effects of endurance exercise training, strength training
increases muscle glucose transporter isoform 4 (GLUT4), but in contrast, mitochondria
numbers do not increase. We hypothesize (1) that strength training in persons with
pre-diabetes may be effective in reversing insulin resistance by novel mechanisms that are
distinct from the endurance training-induced mitochondrial biogenesis. We further
hypothesize (2) that resistance exercise training enhances whole body insulin action
primarily by increasing the white fiber size via the protein kinase mammalian target of
rapamycin (mTOR) and improves insulin-stimulated glucose uptake by increased GLUT4
expression primarily in white fibers of the trained muscles. In this proposal, we will
perform eight weeks of progressive strength training on ten subjects with the Metabolic
Syndrome who are at high risk for developing type 2 diabetes and on ten sedentary control
subjects. This project builds on our experience with a study of focused resistance training
whose results are presented in this application. In this pilot study, subjects exercised on
stationary bicycles for six weeks causing muscle GLUT4 and phopho-mTOR to increase
substantially, but maximal oxygen uptake (VO2max), phospho-AMP-activated protein kinase
(AMPK), peroxisome proliferator-activated receptor-γ co-activator (PGC-1α), and
mitochondrial markers did not change. Our hypotheses will be tested by two Specific Aims.
(1) Subjects at high risk for diabetes will undergo progressively increasing intensity
resistance exercise training and increased strength and improved insulin responsiveness will
both be quantified to demonstrate significant benefit, and (2) quantify the effect of
resistance exercise training on anatomic and functional adaptation in muscle. We will
characterize fiber type, fiber size, fiber-specific changes in mitochondrial DNA and
enzymes, fiber-specific changes in the principle glucose transporters in muscle (GLUT4,
GLUT5, and GLUT12), and evaluate changes in two distinct intramuscular pathways (AMPK, mTOR)
and regulatory factors (PGC-1α, PPARγ, PPARδ) using immunoblots of muscle subcellular
fractions and immunohistochemical techniques. These evaluations of molecular mechanisms will
also include assessing changes in full human Affymetrix gene array data that may move us to
new potential resistance training-regulated gene targets. It is the long-term goal of this
team of investigators to understand the interplay between life style changes and
pharmacological agents in the prevention and treatment of diabetes. Our results will
facilitate the development of more effective clinical options to turn back the epidemic of
obesity and diabetes in the United States.
cornerstones of the treatment of this condition. Both aerobic and resistance exercise
improve diabetes blood glucose control and insulin resistance. These two types of exercise
appear to exert their effects on different muscle fiber types - red for endurance and white
for strength. Similar to the effects of endurance exercise training, strength training
increases muscle glucose transporter isoform 4 (GLUT4), but in contrast, mitochondria
numbers do not increase. We hypothesize (1) that strength training in persons with
pre-diabetes may be effective in reversing insulin resistance by novel mechanisms that are
distinct from the endurance training-induced mitochondrial biogenesis. We further
hypothesize (2) that resistance exercise training enhances whole body insulin action
primarily by increasing the white fiber size via the protein kinase mammalian target of
rapamycin (mTOR) and improves insulin-stimulated glucose uptake by increased GLUT4
expression primarily in white fibers of the trained muscles. In this proposal, we will
perform eight weeks of progressive strength training on ten subjects with the Metabolic
Syndrome who are at high risk for developing type 2 diabetes and on ten sedentary control
subjects. This project builds on our experience with a study of focused resistance training
whose results are presented in this application. In this pilot study, subjects exercised on
stationary bicycles for six weeks causing muscle GLUT4 and phopho-mTOR to increase
substantially, but maximal oxygen uptake (VO2max), phospho-AMP-activated protein kinase
(AMPK), peroxisome proliferator-activated receptor-γ co-activator (PGC-1α), and
mitochondrial markers did not change. Our hypotheses will be tested by two Specific Aims.
(1) Subjects at high risk for diabetes will undergo progressively increasing intensity
resistance exercise training and increased strength and improved insulin responsiveness will
both be quantified to demonstrate significant benefit, and (2) quantify the effect of
resistance exercise training on anatomic and functional adaptation in muscle. We will
characterize fiber type, fiber size, fiber-specific changes in mitochondrial DNA and
enzymes, fiber-specific changes in the principle glucose transporters in muscle (GLUT4,
GLUT5, and GLUT12), and evaluate changes in two distinct intramuscular pathways (AMPK, mTOR)
and regulatory factors (PGC-1α, PPARγ, PPARδ) using immunoblots of muscle subcellular
fractions and immunohistochemical techniques. These evaluations of molecular mechanisms will
also include assessing changes in full human Affymetrix gene array data that may move us to
new potential resistance training-regulated gene targets. It is the long-term goal of this
team of investigators to understand the interplay between life style changes and
pharmacological agents in the prevention and treatment of diabetes. Our results will
facilitate the development of more effective clinical options to turn back the epidemic of
obesity and diabetes in the United States.
Inclusion Criteria:
obese family history of diabetes
Exclusion Criteria:
non-obese diabetes
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