Exogenous endothelin-1 infusion reduced whole-body glucose uptake by 31 +/- 7% (P < 0.05) compared with control, inducing peripheral insulin resistance without decreasing skeletal muscle blood flow.
Does intravenous endothelin-1 reduce peripheral insulin sensitivity in healthy humans?
Exogenous endothelin-1 induces insulin resistance in healthy humans by reducing insulin-dependent glucose uptake in skeletal muscle without decreasing skeletal muscle blood flow.
Estimación del efecto: 31 +/- 7% decrease
valor p: p=< 0.05
In states of insulin resistance, increased plasma levels of endothelin-1 and a disturbed vascular reactivity have been reported. In order to investigate the effects of endothelin-1 on peripheral insulin sensitivity and the vasoactive interactions between insulin and endothelin-1, six healthy subjects were studied on two different occasions with the euglycaemic hyperinsulinaemic clamp technique combined with an intravenous infusion of either endothelin-1 (4 pmol kg-1 min-1) or 0.9% sodium chloride. During the endothelin-1 infusion, arterial plasma endothelin-1 levels rose 10-fold. The endothelin-1 infusion reduced insulin sensitivity as demonstrated by a 31 +/- 7% decrease in whole-body glucose uptake (P < 0.05) and a 26 +/- 11% fall in leg glucose uptake (P < 0.05) compared with the control protocol. During the state of hyperinsulinaemia, exogenous endothelin-1 increased mean arterial blood pressure by 8 +/- 1% (P < 0.05) and decreased splanchnic and renal blood flow by 30 +/- 6% (P < 0.001) and 20 +/- 4% (P < 0.001), respectively. However, the endothelin-1 infusion did not lower skeletal muscle blood flow measured as leg and forearm blood flow. In summary, exogenous endothelin-1 induced insulin resistance in healthy humans by reducing insulin-dependent glucose uptake in skeletal muscle without decreasing skeletal muscle blood flow. Furthermore, endothelin-1 also preserved its vasoactive potency in the presence of hyperinsulinaemia.
Ottosson-Seeberger et al. (Mon,) conducted a other in Healthy (n=6). Endothelin-1 vs. 0.9% sodium chloride was evaluated on Whole-body glucose uptake (31 +/- 7% decrease, p=< 0.05). Exogenous endothelin-1 infusion reduced whole-body glucose uptake by 31 +/- 7% (P < 0.05) compared with control, inducing peripheral insulin resistance without decreasing skeletal muscle blood flow.