Endothelin-1 infusion reduces splanchnic glucose production in humans

Abstract

Two groups of six healthy subjects received an intravenous endothelin-1 (ET-1) infusion (4 pmol.kg-1.min-1 for 20 min) in the basal state. Blood was drawn from catheters in an artery (n = 12), a hepatic vein (n = 12), and a renal vein (n = 6) for determinations of blood flows and substrate exchanges. During the ET-1 infusion, splanchnic and renal blood flows were reduced by approximately 50 (P < 0.01) and 25% (P < 0.001), respectively. Arterial glucose concentration and splanchnic glucose production fell by approximately 4 (P < 0.01) and 55% (P < 0.001), respectively. The latter was still 30% below basal level 3 h after the infusion (P < 0.001). Arterial glycerol increased by 64% (P < 0.01), whereas arterial lactate was unchanged. Splanchnic uptakes of lactate and glycerol were unchanged. Arterial insulin and glucagon showed transient falls with a maximal drop of approximately 35% (P < 0.001) during the infusion. In conclusion, ET-1 infusion causes reduced splanchnic glucose production due to reduced glycogen-derived glucose release. The latter could partly be connected with the transient fall in arterial glucagon, but the prolonged suppressive effect on splanchnic glycogenolysis seems to be linked with other ET-1-related factors. We propose that the underlying mechanism to the transient falls in both arterial glucagon and insulin might be coupled to the ET-1-arginine-NO system.