<原著>Dexamethasone誘発インスリン抵抗性状態でのinsulin-like growth factor 1(IGF-1)の作用 : 全身糖処理に対するインスリン作用とIGF-1作用の解離

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Insulin-like growth factor-1 (IGF-1) is structurally analogous to proinsulin. Upon binding to IGF-1 receptor which is highly homologous to insulin receptor, IGF-1 exerts insulin-like effects. IGF-1 stimulates cellular uptake of glucose and amino acids, increases m RNA and promotes protein synthesis. IGF-1 is known to possess hypoglycemic potency 1/100 to 1/10 of that of insulin when infused into humans. Although IGF-1 and insulin share many intracellular metabolic signaling pathways, it is known that dissociation of their effects can occur in several conditions. In order to test whether glucocorticoids impair the effects of IGF-1 as well as insulin on glucose metabolism, we compared their effects on hepatic glucose output (HGO) and peripheral glucose uptake in vivo in normal control rats and dexamethasone (Dex)-treated rats. Rats were injected Dex (0.1mg/kg) or saline subcutaneously for 4 days before the glucose clamp experiments. Glucose clamp studies coupled with 3-3H-glucose infusion were carried with chronically catheterized rats after an overnight fast. There were 4 groups of rats. The control rats received either insulin infusion (C+Ins, n=7) or IGF-1 infusion (C+IGF-1,n=8). Similarly the Dex-treated rats received insulin (D+Ins, n=8) or IGF-1 infusion (D+IGF-1,n=8). Insulin and IGF-1 were infused at a rate of 8mU/kg/min and 12 μg/kg/min, respectively. These infusion rates were chosen so as to yield the equivalent glucose infusion rate (GIR) during the glucose clamp in the normal control rats. Plasma glucose level was clamped at 110 mg/dl by exogenous glucose infusion. Basal HGO was increased by the treatment with Dex (D+Ins ; 17.7±1.4 mg/kg/min, D+IGF-1 ; 17.4±1.0 mg/kg/min vs C+Ins ; 9.3±0.3 mg/kg/min, C+IGF-1 ; 10.2±0.5 mg/kg/min). Insulin infusion suppressed HGO in the control rats (C+Ins ; 5.8±1.1 mg/kg/min) while it did not decrease HGO in the Dex-treated rats (D+Ins ; 14.6±2.1 mg/kg/min). IGF-1 had no effect on HGO in the control and Dex-treated
岐阜大学の論文
2002-11-30

<原著>Dexamethasone誘発インスリン抵抗性状態でのinsulin-like growth factor 1(IGF-1)の作用 : 全身糖処理に対するインスリン作用とIGF-1作用の解離

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