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Endothelin-1 infusion reduces splanchnic glucose production in humans
G Ahlborg1, E Weitzberg, J M Lundberg
1Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
Insights
Intravenous endothelin-1 (ET-1) infusion significantly reduced splanchnic blood flow and glucose production in healthy subjects. This suggests ET-1 impacts glucose metabolism, potentially through the ET-1-arginine-NO system.
Area of Science:
- Cardiovascular Physiology
- Metabolic Regulation
- Endocrinology
Background:
- Endothelin-1 (ET-1) is a potent vasoconstrictor peptide with known cardiovascular effects.
- The impact of ET-1 on splanchnic glucose production and hormonal regulation is not fully elucidated.
Purpose of the Study:
- To investigate the effects of intravenous endothelin-1 (ET-1) infusion on splanchnic and renal hemodynamics, glucose metabolism, and hormonal responses in healthy humans.
Main Methods:
- Healthy subjects received intravenous ET-1 infusion.
- Blood samples were collected from arterial, hepatic, and renal veins.
- Measurements included blood flows and substrate exchanges, arterial glucose, glycerol, lactate, insulin, and glucagon concentrations.
Main Results:
- ET-1 infusion significantly reduced splanchnic and renal blood flows.
- Splanchnic glucose production decreased markedly and remained suppressed post-infusion.
- Arterial glycerol increased, while insulin and glucagon levels showed transient falls.
Conclusions:
- ET-1 infusion suppresses splanchnic glucose production, primarily via reduced glycogenolysis.
- The prolonged effect on glycogenolysis may involve ET-1-specific factors.
- Transient hormonal changes suggest a link between ET-1, the arginine-nitric oxide pathway, and insulin/glucagon secretion.
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.