Insulin-nonspecific reduction in skeletal muscle glucose transport in high-fat-fed rats

Koshinaka, Keiichi; Oshida, Yoshiharu; Han, Yan-Qing; Kubota, Masakazu; Viana, Amelia Y.I.; Nagasaki, Masaru; Sato, Yuzo

doi:10.1016/j.metabol.2003.12.026

Cited by 8 publications

(8 citation statements)

References 48 publications

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“…In the present study, Akt phosphorylation in response to insulin stimulus in muscle of HFD-fed rats did not decrease at rest or after exercise despite the blunted insulin-dependent GT. This result is consistent with a previous study showing that muscle insulin resistance induced by an HFD is not accompanied by impairment of Akt activation [40] and with studies demonstrating that the postexercise increase in insulin sensitivity does not accompany an enhancement of the insulin signal [22,39,41,42]. We conclude that some functional changes in the GLUT4 translocation system or signal transduction mechanism distal to Akt phosphorylation play a role in HFD-induced insulin resistance and impaired postexercise increase in insulin sensitivity.…”

Section: Discussionsupporting

confidence: 93%

High-fat diet impairs the effects of a single bout of endurance exercise on glucose transport and insulin sensitivity in rat skeletal muscle

Tanaka¹,

Hayashi²,

Toyoda³

et al. 2007

Metabolism

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A single bout of exercise increases the rate of muscle glucose transport (GT) by both insulin-independent and insulin-dependent mechanisms. The purpose of this study was to determine whether high-fat diet (HFD) feeding interferes with the metabolic activation induced by moderate-intensity endurance exercise. Rats were fed an HFD or control diet (CD) for 4 weeks and then exercised on a treadmill for 1 hour (19 m/min, 15% incline). Insulin-independent GT was markedly higher in soleus muscle dissected immediately after exercise than in muscle dissected from sedentary rats in both dietary groups, but insulin-independent GT was 25% lower in HFD-fed than in CD-fed rats. Insulin-dependent GT in the presence of submaximally effective concentration of insulin (0.9 nmol/L) was also higher in both dietary groups in muscle dissected 2 hours after exercise, but was 25% lower in HFD-fed than in CD-fed rats. Exercise-induced activation of 5'adenosine monophosphate-activated protein kinase, a signaling intermediary leading to insulin-independent GT and regulating insulin sensitivity, was correspondingly blunted in the HFD group. High-fat diet did not affect glucose transporter 4 content or insulin-stimulated Akt phosphorylation. Our findings provide evidence that an HFD impairs the effects of short-term endurance exercise on glucose metabolism and that exercise does not fully compensate for HFD-induced insulin resistance in skeletal muscle. Although the underlying mechanism is unclear, reduced 5'adenosine monophosphate-activated protein kinase activation during exercise may play a role.

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Section: Discussionsupporting

confidence: 93%

High-fat diet impairs the effects of a single bout of endurance exercise on glucose transport and insulin sensitivity in rat skeletal muscle

Tanaka¹,

Hayashi²,

Toyoda³

et al. 2007

Metabolism

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“…The effect of PPAR-␦ agonists on GLUT-4 mRNA expression in skeletal muscle is equivocal (23,43). Similarly, the effect of a high-fat diet on muscle GLUT4 protein is controversial (21,25,36,46). We found no influence of either high-fat diet or agonist on total GLUT4 protein in the present study.…”

Section: Glucose Homeostasis and Skeletal Muscle Insulin-stimulated Gcontrasting

confidence: 69%

Oral administration of a PPAR-δ agonist to rodents worsens, not improves, maximal insulin-stimulated glucose transport in skeletal muscle of different fibers

Cresser

Bonen

Chabowski

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Agonists targeting the nuclear receptor peroxisome proliferator-activated receptors (PPAR)-delta may be potential therapeutic agents for insulin-resistant related conditions, as they may be able to stimulate fatty acid (FA) oxidation and attenuate the accumulation of harmful lipid species in skeletal muscle. Several reports have demonstrated that PPAR-delta agonists improve whole body insulin sensitivity. However, whether these agonists exert their direct effects on glucose and FA metabolism in skeletal muscle, and specifically with different fiber types, is unknown. This study was undertaken to determine the effects of oral treatment with the PPAR-delta agonist, GW 501516, in conjunction with the administration of a high-saturated-fat diet on insulin-stimulated glucose transport in isolated oxidative (soleus) and glycolytic (epitrochlearis) rodent skeletal muscle in vitro. High-fat feeding significantly decreased maximal insulin-stimulated glucose transport in soleus, but not epitrochlearis muscle, and was associated with increased skeletal muscle diacylglycerol and ceramide content. Unexpectedly, treatment with the PPAR-delta agonist significantly reduced insulin-stimulated glucose transport in both soleus and epitrochlearis muscles, regardless of dietary fat content. The reduction in insulin-stimulated glucose transport induced by the agonist was associated with large increases in total muscle fatty acid translocase (FAT)/CD36protein content, but not diacylglycerol or ceramide contents. Agonist treatment did not alter the protein content of PPAR-delta, GLUT4, or insulin-signaling proteins (IRS-1, p85 PI3-K, Akt). Agonist treatment led to a small, but significant increase, in the oxidative capacity of glycolytic but not oxidative muscle. We propose that chronic treatment with the PPAR-delta agonist GW 501516 may induce or worsen insulin resistance in rodent skeletal muscle by increasing the capacity for FA transport across the sarcolemma without a sufficient compensatory increase in FA oxidation. However, an accumulation of diacylglycerol and ceramide, while associated with diet-induced insulin resistance, does not appear to be responsible for the agonist-induced reduction in insulin-stimulated glucose transport.

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“…Recent evidence suggests that this lipotoxic effect of FFAs leads to decreased insulin-stimulated skeletal muscle glucose transport [8] , promotes gluconeogenesis and glycogenolysis [9,10] , and causes some impairments and changes in insulin signaling and adipocytokines [11][12][13][14] . Both an acute elevation in plasma FFA via intravenous infusion of lipid emulsion and a chronic elevation in plasma FFA via high-fat feeding in rodents have been shown to induce skeletal muscle and liver insulin resistance [15][16][17] . Hence, lipid plus heparin infusion is thought to induce insulin resistance with similar metabolic characteristics to chronic high-fat feeding [5,15] .…”

Section: Introductionmentioning

confidence: 99%

High-Fat- and Lipid-Induced Insulin Resistance in Rats: The Comparison of Glucose Metabolism, Plasma Resistin and Adiponectin Levels

Yang

et al. 2006

Ann Nutr Metab

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Aims: In animal models, both an acute elevation in plasma free fatty acid (FFA) via intravenous infusion of a lipid emulsion and a chronic elevation in plasma FFA via high-fat feeding have been shown to induce skeletal muscle and liver insulin resistance. However, there have been very few studies comparing the effects of high-fat- and lipid-induced insulin resistance on glucose metabolism and adipocytokines. Methods: In the current study, we used lipid infusion and a high-fat feed in combination with the hyperinsulinemic-euglycemic clamp technique to assess the impact of acute and chronically elevated FFA levels on overall glucose metabolism and insulin action; two adipocytokines, resistin and adiponectin, were used. Results: At baseline, plasma FFA levels were significantly increased in the high-fat diet (HF) group compared to the control group (p < 0.05). During clamp steady-state, the FFA levels were reduced by ∼25% in the control and ∼48% in the HF groups. In contrast, there was a significant increase in the plasma FFA level in the lipid-infused group (from 0.82 ± 0.03 to 2.87 ± 0.18 mmol/l). The glucose infusion rates (GIRs) in the HF and lipid groups were obviously lower than in the control group (p < 0.01). Moreover, GIR was lower in the lipid group compared with the HF group (p < 0.05). The rate of glucose disappearance (G_Rd) was significantly lower in the lipid group compared with the control group. Hepatic glucose production in the control group was suppressed by ∼15% compared with the HF and lipid groups where it was suppressed by only ∼72 and ∼91%, respectively. The resistin level of muscle tissues in the lipid group was significantly higher compared with the control and HF groups (both p < 0.05). After the insulin clamp, the circulating adiponectin level was significantly decreased in the lipid group compared with the control and HF groups (p < 0.05). Conclusions: Lipid infusion, which was more effective than a high-fat diet, can induce peripheral and hepatic insulin resistance in rats. Insulin-induced resistance might be associated with elevated resistin and decreased adiponectin.

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Insulin-nonspecific reduction in skeletal muscle glucose transport in high-fat-fed rats

Cited by 8 publications

References 48 publications

High-fat diet impairs the effects of a single bout of endurance exercise on glucose transport and insulin sensitivity in rat skeletal muscle

High-fat diet impairs the effects of a single bout of endurance exercise on glucose transport and insulin sensitivity in rat skeletal muscle

Oral administration of a PPAR-δ agonist to rodents worsens, not improves, maximal insulin-stimulated glucose transport in skeletal muscle of different fibers

High-Fat- and Lipid-Induced Insulin Resistance in Rats: The Comparison of Glucose Metabolism, Plasma Resistin and Adiponectin Levels

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