[Possible involvement of IGF-1 receptor and IGF-binding protein in insulin-induced enhancement of noradrenaline response in diabetic rat aorta].
The aim of the present study was to investigate the link between the changes in vascular responsiveness associated with hyperinsulinemia in established STZ-induced diabetes and the growth factors signal system. We have shown that in rats with established diabetes, high-insulin treatment can enhances NA-induced contractility. This enhancement probably results from an upregulation of the expression of the mRNA for the alpha 1B- or alpha 1D-adrenergic receptor that is secondary to the hyperinsulinemia. The above effects may be made possible as a result of the increase in IGF-1 receptors and the decreased IGFBPs expressions that occur in the aorta in long-term insulin deficiency. In contrast, those insulin treatments can normalise the impaired endothelium-dependent relaxation, probably by inducing an overexpression of eNOS and VEGF. Furthermore, the expression of the IGF-1 receptor was higher in the aorta in insulin-treated diabetic than in untreated diabetes. This presumably increased the expression of VEGF mRNA, and the increased VEGF presumably upregulated eNOS, thereby resulting in an amelioration in the endothelial dysfunction otherwise seen in diabetic rats. The downside is that such a perturbation of the activity in the IGF-1 system in diabetes could be a key event in the progress of arteriosclerosis and hypertension in syndromes involving hyperinsulinemia.
Kobayashi
Tsuneo
T
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Matsumoto
Takayuki
T
Kamata
Katsuo
K
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D017526:Receptor, IGF Type 1; D004837:Epinephrine