Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats

Brozinick, Joseph T.; Etgen, Garret J.; Yaspelkis, Ben B.; Kang, Hoyoul; Ivy, John L.

doi:10.1152/ajpendo.1993.265.3.e419

Cited by 85 publications

(99 citation statements)

References 20 publications

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“…The PGC-1␣-mediated increase in insulin-stimulated glucose transport (ϩ20% to ϩ38%) is well within the increase observed for insulin-stimulated glucose transport after acute exercise (ϩ12 to ϩ129%) or after 6 -8 weeks of exercise training (ϩ10 to ϩ100%) (74,75). Thus, ours is the first study to demonstrate that a modest PGC-1␣ overexpression in skeletal muscle increased insulin sensitivity in this tissue.…”

Section: Pgc-1␣-induced Fatty Acid Oxidation-supporting

confidence: 82%

Modest PGC-1α Overexpression in Muscle in Vivo Is Sufficient to Increase Insulin Sensitivity and Palmitate Oxidation in Subsarcolemmal, Not Intermyofibrillar, Mitochondria

Benton

Nickerson

Lally

et al. 2008

Journal of Biological Chemistry

198

237

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PGC-1␣ overexpression in skeletal muscle, in vivo, has yielded disappointing and unexpected effects, including disrupted cellular integrity and insulin resistance. These unanticipated results may stem from an excessive PGC-1␣ overexpression in transgenic animals. Therefore, we examined the effects of a modest PGC-1␣ overexpression in a single rat muscle, in vivo, on fuel-handling proteins and insulin sensitivity. We also examined whether modest PGC-1␣ overexpression selectively targeted subsarcolemmal (SS) mitochondrial proteins and fatty acid oxidation, because SS mitochondria are metabolically more plastic than intermyofibrillar (IMF) mitochondria. Among metabolically heterogeneous rat hindlimb muscles, PGC-1␣ was highly correlated with their oxidative fiber content and with substrate transport proteins (GLUT4, FABPpm, and FAT/ CD36) and mitochondrial proteins (COXIV and mTFA) but not with insulin-signaling proteins (phosphatidylinositol 3-kinase, IRS-1, and Akt2), nor with 5-AMP-activated protein kinase, ␣2 subunit, and HSL. Transfection of PGC-1␣ into the red (RTA) and white tibialis anterior (WTA) compartments of the tibialis anterior muscle increased PGC-1␣ protein by 23-25%. This also induced the up-regulation of transport proteins (FAT/CD36, 35-195%; GLUT4, 20 -32%) and 5-AMP-activated protein kinase, ␣2 subunit (37-48%), but not other proteins (FABPpm, IRS-1, phosphatidylinositol 3-kinase, Akt2, and HSL). SS and IMF mitochondrial proteins were also up-regulated, including COXIV (15-75%), FAT/CD36 (17-30%), and mTFA (15-85%). PGC-1␣ overexpression also increased palmitate oxidation in SS (RTA, ؉116%; WTA, ؉40%) but not in IMF mitochondria, and increased insulin-stimulated phosphorylation of AKT2 (28 -43%) and rates of glucose transport (RTA, ؉20%; WTA, ؉38%). Thus, in skeletal muscle in vivo, a modest PGC-1␣ overexpression up-regulated selected plasmalemmal and mitochondrial fuel-handling proteins, increased SS (not IMF) mitochondrial fatty acid oxidation, and improved insulin sensitivity.

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Section: Pgc-1␣-induced Fatty Acid Oxidation-supporting

confidence: 82%

Modest PGC-1α Overexpression in Muscle in Vivo Is Sufficient to Increase Insulin Sensitivity and Palmitate Oxidation in Subsarcolemmal, Not Intermyofibrillar, Mitochondria

Benton

Nickerson

Lally

et al. 2008

Journal of Biological Chemistry

198

237

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“…The locus of this insulin resistance is thought to reside in the glucose transport process [22,23]. In the present study, troglitazone resulted in increased insulin-stimulated glucose uptake, insulin sensitivity, and muscle glycogen content in Zucker obese rats.…”

Section: Discussionsupporting

confidence: 49%

Troglitazone Improves Insulin-Stimulated Glucose Utilization Associated with an Increased Muscle Glycogen Content in Obese Zucker Rats.

et al. 1999

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“…In obesity, total muscle GLUT4 content is not altered, but insulin-induced GLUT4 translocation is impaired (9,20,52), and thus plasmalemmal GLUT4 is reduced. Clearly, the cycling of transport proteins between the muscle's surface and intracellular depots is an important mechanism regulating substrate transport rates.…”

Section: Intracellular Cycling Of Lcfa Transportersmentioning

confidence: 98%

Different mechanisms can alter fatty acid transport when muscle contractile activity is chronically altered

Koonen

Benton²,

Arumugam³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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. Different mechanisms can alter fatty acid transport when muscle contractile activity is chronically altered. Am J Physiol Endocrinol Metab 286: E1042-E1049, 2004; 10.1152/ajpendo.00531.2003.-We examined whether skeletal muscle transport rates of long-chain fatty acids (LCFAs) were altered when muscle activity was eliminated (denervation) or increased (chronic stimulation). After 7 days of chronically stimulating the hindlimb muscles of female Sprague-Dawley rats, the LCFA transporter proteins fatty acid translocase (FAT)/CD36 (ϩ43%) and plasma membrane-associated fatty acid-binding protein (FABPpm; ϩ30%) were increased (P Ͻ 0.05), which resulted in the increased plasmalemmal content of these proteins (FAT/CD36, ϩ42%; FABPpm ϩ13%, P Ͻ 0.05) and a concomitant increase in the LCFA transport rate into giant sarcolemmal vesicles (ϩ44%, P Ͻ 0.05). Although the total muscle contents of FAT/CD36 and FABPpm were not altered (P Ͼ 0.05) after 7 days of denervation, the LCFA transport rate was markedly decreased (Ϫ39%). This was associated with reductions in plasmalemmal FAT/CD36 (Ϫ24%) and FABPpm (Ϫ28%; P Ͻ 0.05). These data suggest that these LCFA transporters were resequestered to their intracellular depot(s) within the muscle. Combining the results from these experiments indicated that changes in rates of LCFA transport were correlated with concomitant changes in plasmalemmal FAT/CD36 and FABPpm, but not necessarily with their total muscle content. Thus chronic alterations in muscle activity can alter the rates of LCFA transport via different mechanisms, either 1) by increasing the total muscle content of FAT/CD36 and FABPpm, resulting in a concomitant increase at the sarcolemma, or 2) by reducing the plasma membrane content of these proteins in the absence of any changes in their total muscle content. giant vesicles; tibialis anterior; gastrocnemius; denervation; chronic stimulation SKELETAL MUSCLES depend on long-chain fatty acids (LCFAs) to maintain ATP production during contractile activity. When muscle activity is increased, progressively more LCFAs are taken up into the muscle (16). It is now recognized that LCFAs cross the sarcolemma via simple diffusion and a proteinmediated system (3,4,35,47). Several proteins have been identified as LCFA transporters. Fatty acid translocase (FAT/ CD36) and plasma membrane-associated fatty acid-binding protein (FABPpm) have been shown to facilitate LCFA transport into heart and skeletal muscle (3, 24, 38, 47), whereas fatty acid transport protein 1 (FATP1) appears to be involved in the transport of LCFAs and acylating very long-chain fatty acids (15,45,53,58).Skeletal muscle metabolism is remarkably capable of adapting to changes in muscle activity pattern (7, 44a). Chronic changes in muscle activity can also alter the expression of several substrate transporters, and hence substrate transport. For example, increasing muscle activity by chronic stimulation enhances glucose and lactate transport and their respective transporters GLUT4 (28,46,56) and the monocarboxylate transp...

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Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats

Cited by 85 publications

References 20 publications

Modest PGC-1α Overexpression in Muscle in Vivo Is Sufficient to Increase Insulin Sensitivity and Palmitate Oxidation in Subsarcolemmal, Not Intermyofibrillar, Mitochondria

Modest PGC-1α Overexpression in Muscle in Vivo Is Sufficient to Increase Insulin Sensitivity and Palmitate Oxidation in Subsarcolemmal, Not Intermyofibrillar, Mitochondria

Troglitazone Improves Insulin-Stimulated Glucose Utilization Associated with an Increased Muscle Glycogen Content in Obese Zucker Rats.

Different mechanisms can alter fatty acid transport when muscle contractile activity is chronically altered

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