Rosiglitazone Enhances Glucose Tolerance by Mechanisms Other than Reduction of Fatty Acid Accumulation within Skeletal Muscle

Lessard, Sarah J.; Giudice, Sonia L. Lo; Lau, Winnie Ak; Reid, Julianne J.; Turner, Nigel; Febbraio, Mark A.; Hawley, John A.; Watt, Matthew James

doi:10.1210/en.2004-0659

Cited by 52 publications

(58 citation statements)

References 44 publications

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“…Analysis of intramuscular muscle lipids. Skeletal muscle triacylglycerol (TAG), diacylglycerol (DAG), and ceramide contents were determined as outlined previously (12). Blood metabolite measurements.…”

Section: Methodsmentioning

confidence: 99%

“…that by increasing fatty acid storage in adipose tissue, TZDs enhance insulin sensitivity by reducing the toxic accumulation of lipids in other insulin-sensitive tissues such as skeletal muscle and liver (5). However, there is mounting evidence that rosiglitazone acts to improve insulin sensitivity in the absence of decreased muscle lipid storage in humans (9,27) and animal models of insulin resistance (7,10,12,28), suggesting that lipid steal from muscle may not be necessary for rosiglitazone-induced insulin sensitization. Although some investigations have demonstrated that lipid storage is decreased in muscle after rosiglitazone treatment (3,4,24), rosiglitazone-induced reductions of liver lipid accumulation have been more consistently observed (5,7,9,29).…”

Section: Fig 3 Skeletal Muscle Ampk Activity and Protein Expressionmentioning

confidence: 99%

“…However, the sequestration of lipids from skeletal muscle after chronic rosiglitazone treatment has not been consistently observed (3)(4)(5)(6)(7)(8)(9)(10)(11). There is also evidence that mechanism(s) independent of changes in lipid status (i.e., skeletal muscle AMP-activated protein kinase [AMPK] activation) may be involved in the insulinsensitizing actions of rosiglitazone (12,13). Exercise training also induces several adaptations that may promote glucose uptake and fatty acid oxidation in skeletal muscle, including increased mitochondrial biogenesis, improved insulin signal transduction, and elevated GLUT4 protein content (14,15).…”

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confidence: 99%

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Tissue-Specific Effects of Rosiglitazone and Exercise in the Treatment of Lipid-Induced Insulin Resistance

et al. 2007

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Both pharmacological intervention (i.e., thiazolidinediones [TZDs]) and lifestyle modification (i.e., exercise training) are clinically effective treatments for improving whole-body insulin sensitivity. However, the mechanism(s) by which these therapies reverse lipid-induced insulin resistance in skeletal muscle is unclear. We determined the effects of 4 weeks of rosiglitazone treatment and exercise training and their combined actions (rosiglitazone treatment and exercise training) on lipid and glucose metabolism in high-fat-fed rats. High-fat feeding resulted in decreased muscle insulin sensitivity, which was associated with increased rates of palmitate uptake and the accumulation of the fatty acid metabolites ceramide and diacylglycerol. Impairments in lipid metabolism were accompanied by defects in the Akt/AS160 signaling pathway. Exercise training, but not rosiglitazone treatment, reversed these impairments, resulting in improved insulinstimulated glucose transport and increased rates of fatty acid oxidation in skeletal muscle. The improvements to glucose and lipid metabolism observed with exercise training were associated with increased AMP-activated protein kinase ␣1 activity; increased expression of Akt1, peroxisome proliferator-activated receptor ␥ coactivator 1, and GLUT4; and a decrease in AS160 expression. In contrast, rosiglitazone treatment exacerbated lipid accumulation and decreased insulin-stimulated glucose transport in skeletal muscle. However, rosiglitazone, but not exercise training, increased adipose tissue GLUT4 and acetyl CoA carboxylase expression. Both exercise training and rosiglitazone decreased liver triacylglycerol content. Although both interventions can improve whole-body insulin sensitivity, our results show that they produce divergent effects on protein expression and triglyceride storage in different tissues. Accordingly, exercise training and rosiglitazone may act as complementary therapies for the treatment of insulin resistance.

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Section: Methodsmentioning

confidence: 99%

Section: Fig 3 Skeletal Muscle Ampk Activity and Protein Expressionmentioning

confidence: 99%

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confidence: 99%

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Tissue-Specific Effects of Rosiglitazone and Exercise in the Treatment of Lipid-Induced Insulin Resistance

et al. 2007

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“…Despite intensive research into the role of PPAR␥, the mechanisms by which their synthetic ligands, the thiazolidinediones (TZDs), cause insulin sensitization are incompletely understood. TZDs improve hepatic insulin sensitivity (196), but interestingly, they do not consistently lower lipid content (288). TZDs activate AMPK in skeletal muscle cells by increasing cellular adenine nucleotide levels (153,277).…”

Section: B Thiazolidinedionesmentioning

confidence: 99%

AMPK in Health and Disease

Steinberg¹,

Kemp²

2009

Physiological Reviews

1,459

1,419

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The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) αβγ heterotrimer has emerged as an important integrator of signals that control energy balance through the regulation of multiple biochemical pathways in all eukaryotes. In this review, we begin with the discovery of the AMPK family and discuss the recent structural studies that have revealed the molecular basis for AMP binding to the enzyme's γ subunit. AMPK's regulation involves autoinhibitory features and phosphorylation of both the catalytic α subunit and the β-targeting subunit. We review the role of AMPK at the cellular level through examination of its many substrates and discuss how it controls cellular energy balance. We look at how AMPK integrates stress responses such as exercise as well as nutrient and hormonal signals to control food intake, energy expenditure, and substrate utilization at the whole body level. Lastly, we review the possible role of AMPK in multiple common diseases and the role of the new age of drugs targeting AMPK signaling.

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“…where PR is the total protein content/mg muscle, TG is the lipid content/mg muscle, GLY is the glycogen content/mg of muscle, W s is the water (and dissolved solutes) content in 1 mg of muscle ( 17 for EDL and SOL in obese and lean rodents, expressed as mg mg À1 muscle using a molecular weight of 800 Da for an average triglyceride and the value of 3.66 for the ratio of muscle (wet) mass/muscle dry mass. 18 For GLY values, we used the EDL and SOL data of Goodman and Stephenson 18 for the EDL and SOL muscles from the lean animals and the ob/ob gastrocnemius muscle data of Kaidanovich-Beilin and EldarFinkelman 19 for all three muscles from obese animals.…”

Section: Muscle Densitymentioning

confidence: 99%

Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse

et al. 2009

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Background: Knowledge of the morphological and biochemical alterations occurring in skeletal muscles of obese animals is relatively limited, particularly with respect to non-limb muscles and relationship to fibre type. Objective: Sternomastoid (SM; fast-twitch), extensor digitorum longus (EDL; fast-twitch), and soleus (SOL; mixed) muscles of ob/ob mouse (18-22 weeks) were examined with respect to size (mass, muscle mass-to-body mass ratio, cross-sectional area (CSA)), fibre CSA, protein content, myosin heavy chain (MHC) content, MHC isoform (MHC i ) composition, MHC i -based fibre type composition, and lactate dehydrogenase isoenzyme (LDH iso ) composition. Results: Compared with (control) muscles from lean mice, all the three muscles from ob/ob mice were smaller in size (by 13-30%), with SM and EDL being the most affected. The CSA of IIB and IIB þ IID fibres (the predominant fibre types in SM and EDL muscles) was markedly smaller (by B30%) in ob/ob mice, consistent with differences in muscle size. Total protein content (normalised to muscle mass) was significantly lower in EDL (À9.7%) and SOL (À14.1%) muscles of ob/ob mice, but there were no differences between SM, EDL, and SOL muscles from the two animal groups with respect to MHC content (also normalised to muscle mass). Electrophoretic analyses of MHC i composition in whole muscle homogenates and single muscle fibres showed a shift towards slower MHC i content, slower MHC i containing fibres, and a greater proportion of hybrid fibres in all the three muscles of ob/ob mice, with a shift towards a more aerobic-oxidative phenotype also observed with respect to LDH iso composition. Conclusion: This study showed that SM, EDL, and SOL muscles of ob/ob mice display size reductions to an extent that seems to be largely related to fibre type composition, and a shift in fibre type composition that may result from a process of structural remodelling, as suggested by the increased proportion of hybrid fibres in muscles of ob/ob mice.

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Rosiglitazone Enhances Glucose Tolerance by Mechanisms Other than Reduction of Fatty Acid Accumulation within Skeletal Muscle

Cited by 52 publications

References 44 publications

Tissue-Specific Effects of Rosiglitazone and Exercise in the Treatment of Lipid-Induced Insulin Resistance

Tissue-Specific Effects of Rosiglitazone and Exercise in the Treatment of Lipid-Induced Insulin Resistance

AMPK in Health and Disease

Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse

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