Changes in glucose transport and protein kinase Cβ 2 in rat skeletal muscle induced by hyperglycaemia

Kawano, Yoshio; Rincón, Jorge; Soler, Aléjandro Peralta; Ryder, Jeffrey W.; Nolte, Lorraine A.; Zierath, Juleen R.; Wallberg-Henriksson, Harriet

doi:10.1007/s001250051273

Cited by 35 publications

(32 citation statements)

References 56 publications

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“…We previously reported that high glucose concentrations interact in a dual way with the insulin signalling cascade; hyperglycaemia induced translocation of GLUT4 in three different muscle-derived model systems [17] and hyperglycaemia induced insulin resistance in rat-1 fibroblasts [19]. In agreement with this, several studies reported an hyperglycaemia-induced increased glucose uptake [18,20]. In this study, we found such an effect on GLUT4 translocation in whole, insulin-resistant animals.…”

Section: Discussionsupporting

confidence: 89%

“…We have previously reported that the PKC isoform b is important for the short-term high glucose effect in muscle [17]. Hyperglycaemia has been shown to induce translocation of PKC-bI and -bII [20]. However, the effect on PKCbI failed to reach statistical significance in the latter study.…”

Section: Discussionmentioning

confidence: 67%

“…Several studies suggested a role of PKC in hyperglycaemia-induced glucose uptake [17,18,20] and in insulin resistant states [19, 25, 57±59]. PKC overexpression or long-term exposure to TPA down regulates IRS-1 expression and leads to insulin resistance [60].…”

Section: Discussionmentioning

confidence: 99%

“…The activation of PKC has been explained by the finding that the high glucoseinduced glucose metabolism leads to increased synthesis of DAG which in turn activates the corresponding PKC isoforms [26]. Short-term hyperglycaemia was reported to activate PKC isoforms in different cells [17, 25±28] and in isolated rat skeletal muscle [17,18,20].…”

mentioning

confidence: 99%

“…It has been shown that activated PKCs are involved in stimulating glucose transport [29±35] and translocation of glucose transporters by a mechanism which is distinct from that of insulin [17,18,20,30,31,35,36]. Other studies have focussed on the effect of PKC on the insulin signalling cascade showing that activation of PKC inhibits insulin-stimulated glucose transport in rat heart and skeletal muscle and rat adipocytes [21,29,37].…”

mentioning

confidence: 99%

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Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle

et al. 2002

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Impairment of the glucose transport in the insulinsensitive tissues contributes to the pathogenesis of Type II (non-insulin-dependent) diabetes mellitus [1,2]. Skeletal muscle represents the most important tissue for the maintenance of a balanced postprandial glucose homeostasis; about 80 % of insulin-stimulated glucose uptake is accounted for by muscle [3±5]. The influx of glucose into muscle is mediated by the glucose transporter proteins GLUT1 and the insulinsensitive GLUT4 [6±11]. Insulin induces the translocation of GLUT4 to the sarcolemma and to special- Abstract Aims/hypothesis. Previous studies on diabetic patients have shown that hyperglycaemia increases glucose uptake in an apparently insulin-independent manner. However, the molecular mechanism has not been clarified. Methods. We studied rats receiving continuous glucose infusion to address this question. In this animal model, rats accommodate systemic glucose oversupply and rapidly develop insulin resistance. Results. Glucose infusion increased both plasma glucose and insulin concentrations to peak after one day. In spite of continuous glucose infusion normoglycaemia was reached after 5 days while insulin concentrations remained higher. Focusing our studies in day 2 (hyperglycaemia/hyperinsulinaemia) and day 5 (normoglycaemia/hyperinsulinaemia) we found, particularly in day 5, that the early steps of the insulin signalling cascade in skeletal muscle of glucose-infused rats were not more activated when compared to control animals as assessed by a comparable phosphorylation of the insulin receptor, IRS-1 and PKB and by an unaltered IRS-1-associated Ptd(Ins) 3' kinase activity. Continuous glucose infusion induced GLUT4 protein expression and translocation to the plasma membrane while neither expression nor translocation of GLUT1 was affected. Translocation of PKC-bI, -bII (> threefold) and -a, -q (to a lesser extent) to the plasma membrane was significantly induced after 2 days but not after 5 days of glucose infusion when normoglycaemia was reached. Conclusions/interpretation. Our data support the hypothesis that continuous glucose infusion induces translocation of GLUT4 while the early steps of the insulin signalling cascade were not increased. These effects could be mediated by activation of PKC. [Diabetologia (2002) 45: 356±368]

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle

et al. 2002

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Metabolic Stress and Atherosclerosis

Reusch

Brownlee

2003

International Textbook of Diabetes Mellitus

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Diabetes is associated with accelerated atherosclerotic macrovascular disease affecting arteries that supply the heart, brain, and lower extremities. As a consequence, patients with diabetes have a much higher risk of myocardial infarction, stroke, and limb amputation. The excess risk associated with diabetes remains even after adjustment for traditional coronary heart disease risk factors such as smoking, hypertension, and hypercholesterolemia. Type 2 diabetic patients without a previous myocardial infarction have as high a risk of myocardial infarction over 7 years as nondiabetic patients with a previous myocardial infarction. Type 1 diabetes results in nearly 100% atherosclerosis by the fifth decade of life. The mechanisms by which diabetes confers this increased risk are much less clear than those responsible for diabetic microvascular disease, but associational studies suggest that the metabolic derangements caused by insulin resistance and insulin deficiency are involved. These include dyslipoproteinemia, excess free fatty acid flux, and hyperglycemia. In this chapter we review recent findings on the mechanisms whereby high glucose and high FFAs, present in both type 1 and type 2 diabetes, lead to vascular dysfunction and injury. Pathways involving advanced glycation end products, protein kinase C, NF‐κB, aldose reductase, hexosamine, and CREB (cAMP response element binding protein) are reviewed. Both hyperglycemia and high free fatty acid flux lead to increased vascular oxidative stress, which appears to activate all of these signaling pathways, leading to diabetic macrovascular disease.

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Macrovascular angiopathy in children and adolescents with type 1 diabetes

Giannini

Mohn

Chiarelli

et al. 2011

Diabetes Metabolism Res

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Diabetes represents one of the most common diseases globally. Worryingly, the worldwide incidence of type 1 diabetes (T1D) is rising by 3% per year. Despite the rapid increase in diabetes incidence, recent advances in diabetes treatment have been successful in decreasing morbidity and mortality from diabetes-related retinopathy, nephropathy, and neuropathy. In contrast, there is clear evidence for the lack of improvement in mortality for cardiovascular diseases (CVDs). This emphasizes the importance of focusing childhood diabetes care strategies for the prevention of CVD in adulthood. Furthermore, although most work on diabetes and macrovascular disease relates to type 2 diabetes, it has been shown that the age-adjusted relative risk of CVD in T1D far exceeds that in type 2 diabetes. As T1D appears predominantly during childhood, those with T1D are at greater risk for coronary events early in life and require lifelong medical attention. Because of the important health effects of CVDs in children and adolescents with T1D, patients, family members, and care providers should understand the interaction of T1D and cardiovascular risk. In addition, optimal cardiac care for the patient with diabetes should focus on aggressive management of traditional cardiovascular risk factors to optimize those well-recognized as well as new specific risk factors which are becoming available. Therefore, a complete characterization of the molecular mechanisms involved in the development and progression of macrovascular angiopathy is needed. Furthermore, as vascular abnormalities begin as early as in childhood, potentially modifiable risk factors should be identified at an early stage of vascular disease development.

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Changes in glucose transport and protein kinase Cβ 2 in rat skeletal muscle induced by hyperglycaemia

Cited by 35 publications

References 56 publications

Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle

Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle

Metabolic Stress and Atherosclerosis

Macrovascular angiopathy in children and adolescents with type 1 diabetes

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