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Acute blockade by endothelin-1 of haemodynamic insulin action in rats


Ross, RM and Kolka, CM and Rattigan, S and Clark, MG, Acute blockade by endothelin-1 of haemodynamic insulin action in rats, Diabetologia, 50, (2) pp. 443-451. ISSN 0012-186X (2007) [Refereed Article]

DOI: doi:10.1007/s00125-006-0525-8


AIMS/HYPOTHESIS: Plasma levels of endothelin-1 are frequently elevated in patients with hypertension, obesity and type 2 diabetes. We hypothesise that this vasoconstrictor may prevent full perfusion of muscle, thereby limiting delivery of insulin and glucose and contributing to insulin resistance. MATERIALS AND METHODS: The acute effects of endothelin-1 on insulin-mediated haemodynamic and metabolic effects were examined in rats in vivo. Endothelin-1 (50 pmol min(-1) kg(-1) for 2.5 h) was infused alone, or 30 min prior to a hyperinsulinaemic-euglycaemic insulin clamp (10 mU min(-1) kg(-1) for 2 h). Insulin clamps (10 or 15 mU min(-1) kg(-1)) were performed after 30 min of saline infusion. RESULTS: Endothelin-1 infusion alone increased plasma endothelin-1 11-fold (p < 0.05) and blood pressure by 20% (p < 0.05). Endothelin-1 alone had no effect on femoral blood flow, capillary recruitment or glucose uptake, but endothelin-1 with 10 mU min(-1) kg(-1) insulin caused a decrease in insulin clearance from 0.35 +/- 0.6 to 0.19 +/- 0.02 ml/min (p = 0.02), resulting in significantly higher plasma insulin levels (10 mU min(-1) kg(-1) insulin: 2,120 +/- 190 pmol/l; endothelin-1 + 10 mU min(-1)kg(-1) insulin: 4,740 +/- 910 pmol/l), equivalent to 15 mU min(-1) kg(-1) insulin alone (4,920 +/- 190 pmol/l). The stimulatory effects of equivalent doses of insulin on femoral blood flow, capillary recruitment and glucose uptake were blocked by endothelin-1. CONCLUSIONS/INTERPRETATION: Endothelin-1 blocks insulin's haemodynamic effects, particularly capillary recruitment, and is associated with decreased muscle glucose uptake and glucose infusion rate. These findings suggest that elevated endothelin-1 levels may contribute to insulin resistance of muscle by increasing vascular resistance and limiting insulin and glucose delivery.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Medical physiology
Research Field:Systems physiology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Ross, RM (Dr Renee Ross)
UTAS Author:Kolka, CM (Miss Cathryn Kolka)
UTAS Author:Rattigan, S (Professor Stephen Rattigan)
UTAS Author:Clark, MG (Professor Michael Clark)
ID Code:49790
Year Published:2007
Web of Science® Times Cited:25
Deposited By:Biochemistry
Deposited On:2007-08-01
Last Modified:2016-08-23

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