ENDOTHELIN-1 INFUSION REDUCES SPLANCHNIC GLUCOSE-PRODUCTION IN HUMANS

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 stat e. Blood was drawn from catheters in an artery (n = 12), a hepatic vei n (n = 12), and a renal vein (n = 6) for determinations of blood flows and substrate exchanges. During the ET-1 infusion, splanchnic and ren al blood flows were reduced by similar to 50 (P < 0.01) and 25% (P < 0 .001), respectively. Arterial glucose concentration and splanchnic glu cose production fell by similar to 4 (P < 0.01) and 55% (P < 0.001), r espectively. The latter was still 30% below basal level 3 h after the infusion (P < 0.001). Arterial glycerol increased by 64% (P < 0.01), w hereas arterial lactate was unchanged. Splanchnic uptakes of lactate a nd glycerol were unchanged. Arterial insulin and glucagon showed trans ient falls with a maximal drop of similar to 35% (P < 0.001) during th e infusion. In conclusion, ET-1 infusion causes reduced splanch- nic g lucose 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 glycogeno lysis seems to be linked with other ET-1-related factors. We propose t hat the underlying mechanism to the transient falls in both arterial g lucagon and insulin might be coupled to the ET-1-arginine-NO system.