A High-fructose Diet Impairs Akt and PKCζ Phosphorylation and GLUT4 Translocation in Rat Skeletal Muscle

Li, P; Koike, Teruhiko; Qin, Bolin; Kubota, Masashi; Kawata, Yuichi; Jia, Yanan; Oshida, Y

doi:10.1055/s-2008-1073162

Cited by 25 publications

(24 citation statements)

References 20 publications

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“…These actions may partially explain our observation of improved insulin sensitivity after CYP2J3 gene delivery. In addition, we observed effects on insulin signaling in tissues directly involved in insulin sensitivity (37–40), including liver, muscle, heart, and kidney, as well as in an islet cell line. Our data show that insulin-dependent signaling was significantly inhibited in fructose-treated rats and db/db mice, but dramatically reversed by CYP2J3 overexpression.…”

Section: Discussionmentioning

confidence: 94%

Increased CYP2J3 Expression Reduces Insulin Resistance in Fructose-Treated Rats and db/db Mice

Zhao

Wang

et al. 2010

Diabetes

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OBJECTIVEAccumulating evidence suggests that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play crucial and diverse roles in cardiovascular homeostasis. The anti-inflammatory, antihypertensive, and pro-proliferative effects of EETs suggest a possible beneficial role for EETs on insulin resistance and diabetes.RESEARCH DESIGN AND METHODSThis study investigated the effects of CYP2J3 epoxygenase gene therapy on insulin resistance and blood pressure in diabetic db/db mice and in a model of fructose-induced hypertension and insulin resistance in rats.RESULTSCYP2J3 gene delivery in vivo increased EET generation, reduced blood pressure, and reversed insulin resistance as determined by plasma glucose levels, homeostasis model assessment insulin resistance index, and glucose tolerance test. Furthermore, CYP2J3 treatment prevented fructose-induced decreases in insulin receptor signaling and phosphorylation of AMP-activated protein kinases (AMPKs) in liver, muscle, heart, kidney, and aorta. Thus, overexpression of CYP2J3 protected against diabetes and insulin resistance in peripheral tissues through activation of insulin receptor and AMPK pathways.CONCLUSIONSThese results highlight the beneficial roles of the CYP epoxygenase-EET system in diabetes and insulin resistance.

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Section: Discussionmentioning

confidence: 94%

Increased CYP2J3 Expression Reduces Insulin Resistance in Fructose-Treated Rats and db/db Mice

Zhao

Wang

et al. 2010

Diabetes

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“…PI3 K is a key enzyme in the insulin signaling pathway [28] , and Akt / PKB is one of its downstream targets. The insulin-stimulated phosphorylation of Akt / PKB via PI3 K is an important indicator of the proper working of insulin [29] . In a high-glucose condition, insulin fails to activate Akt / PKB, producing an insulin-resistant state.…”

Section: Discussion ▼mentioning

confidence: 99%

Amelioration of Insulin Resistance by Scopoletin in High-Glucose-Induced, Insulin-Resistant HepG2 Cells

et al. 2010

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Insulin resistance plays an important role in the development of type 2 diabetes mellitus. Scopoletin, a phenolic coumarin, is reported to regulate hyperglycemia and diabetes. To examine its effect on insulin resistance, we treated high-glucose-induced, insulin-resistant HepG2 cells with scopoletin and measured phosphatidylinositol 3-kinase (PI3 K)-linked protein kinase B (Akt/PKB) phosphorylation. Scopoletin significantly stimulated the reactivation of insulin-mediated Akt/PKB phosphorylation. This effect was blocked by LY294002, a specific PI3 K inhibitor. The ability of scopoletin to activate insulin-mediated Akt/PKB was greater than that of rosiglitazone, a thiazolidinedione, and scopoletin was less adipogenic than rosiglitazone, as shown by the extent of lipid accumulation in differentiated adipocytes. Scopoletin increased the gene expression of both peroxisome proliferator-activated receptor γ2 (PPARγ2), a target receptor for rosiglitazone, and adipocyte-specific fatty acid binding protein, but not to the level induced by rosiglitazone. However, the PPARγ2 protein level was increased equally by rosiglitazone and scopoletin in differentiated adipocytes. Our results suggest that scopoletin can ameliorate insulin resistance in part by upregulating PPARγ2 expression. With its lower adipogenic property, scopoletin may be a useful candidate for managing metabolic disorders, including type 2 diabetes mellitus.

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“…19 In addition, phosphorylation of Akt (protein kinase B) and atypical protein kinase C, both of which are downstream mediators of IRS-1 in insulin signalling pathways, is also decreased in the HFD model. 16 In this study, repeated application of low-frequency EA stimulation improved GIR in the HFD model. Since this model resembles diet-induced insulin resistance in humans, EA may have benefi cial effects on prediabetic patients such as those with metabolic syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…After pulverisation in an iron mortar (Nonaka Rikaki, Tokyo, Japan), specimens were homogenised in HEPES buffer (25 mM HEPES, pH 7.4, 2 mM EDTA, 250 mM sucrose, 1% Triton X-100, 1 mM PMSF) using a polytron homogeniser (PT-3100; KINEMATICA, Lucerne, Switzerland). 16 The insoluble and soluble fractions were centrifuged at 6500 rpm for 30 min at 4°C, and HEPES buffer of an equal volume to that of the soluble fraction was added to the centrifuged insoluble fraction. Protein content of the supernatant was measured using a commercially available kit (#500-0006; Bio-Rad Laboratories, Hercules, California, USA).…”

Section: Muscle Preparationmentioning

confidence: 99%

Repeated Application of Low-Frequency Electroacupuncture Improves High-Fructose Diet-Induced Insulin Resistance in Rats

et al. 2011

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Background Insulin resistance is frequently present in obesity and during the development of type 2 diabetes mellitus. Objective The purpose of the present study was to investigate the effect of electroacupuncture (EA) on high-fructose diet (HFD)-induced insulin resistance. Methods Male Wistar rats were fed HFD for 4 weeks and developed insulin resistance. Insulin sensitivity was assessed by clamp. The number of animals was seven, eight and seven in the control, HFD and HFD+EA groups, respectively. AMPactivated protein kinase (AMPK) and glucose transporter 4 (GLUT4) in skeletal muscle were measured by Western blotting analysis (n=7 in each group). EA stimulation was carried out 12 times over 4 weeks at an intensity of 1-3 mA and a frequency of 2/15 Hz in a conscious state without restraint. Results There was no signifi cant difference in mean body weight and fasting blood glucose concentration between groups at the end of the experiment. The mean glucose infusion rate during the clamp was signifi cantly lower in the HFD group than in controls (p<0.05). There was no signifi cant difference in expression of GLUT4 in skeletal muscle in the control and each group. Phosphorylated AMPKα (Thr 172 ) in skeletal muscle showed a signifi cant increase immediately after the fi nal EA stimulation when compared with the control group (p<0.05). Conclusion Repeated application of EA is capable of improving diet-induced insulin resistance, probably through activation of AMPK signalling pathways in skeletal muscle. These results suggest that repeated application of EA may have benefi cial effects on diet-induced insulin resistance. INTRODUCTIONDiabetes mellitus is a metabolic disorder that can lead to a wide range of complications, including coronary artery disease, cerebrovascular disorders, renal failure, blindness and gangrene. The prevalence of diabetes among adults (aged 20-79 years) in 2010 was estimated to be 6.4%, affecting 285 million adults, and will increase to 7.7% (439 million adults) by 2030. 1Insulin resistance is frequently present in obesity and during the development of type 2 diabetes mellitus and is generally defi ned as a reduction in the body's ability to clear a glucose load from circulation in response to insulin. Although there is controversy regarding the relative importance of insulin resistance and impaired β cell function in the pathogenesis of diabetes, some studies have proposed that loss of early insulin response to glucose and poor suppression of hepatic glucose output are primarily responsible for development of the disease.2 Pharmacological agents that reduce insulin resistance are clinically available, but they carry a potential risk of serious complications.3 4 In the last decade, increasing evidence has suggested that electroacupuncture (EA) may improve glucose metabolism by modifying insulin sensitivity.5 6 Studies have suggested that EA increases insulin secretion and/or enhances insulin sensitivity in diabetic and obese rodent models.5 7 However, the electrical stimulation int...

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A High-fructose Diet Impairs Akt and PKCζ Phosphorylation and GLUT4 Translocation in Rat Skeletal Muscle

Cited by 25 publications

References 20 publications

Increased CYP2J3 Expression Reduces Insulin Resistance in Fructose-Treated Rats and db/db Mice

Increased CYP2J3 Expression Reduces Insulin Resistance in Fructose-Treated Rats and db/db Mice

Amelioration of Insulin Resistance by Scopoletin in High-Glucose-Induced, Insulin-Resistant HepG2 Cells

Repeated Application of Low-Frequency Electroacupuncture Improves High-Fructose Diet-Induced Insulin Resistance in Rats

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