Endothelin limits insulin action in obese/insulin-resistant humans

Amale Lteif, Prashant Vaishnava, Alain D. Baron, Kieren Mather

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

The normal action of insulin to vasodilate and redistribute blood flow in support of skeletal muscle metabolism is impaired in insulin-resistant states. Increased endogenous endothelin contributes to endothelial dysfunction in obesity and diabetes. Here, we test the hypothesis that increased endogenous endothelin action also contributes to skeletal muscle insulin resistance via impairments in insulin-stimulated vasodilation. We studied nine lean and seven obese humans, measuring the metabolic and hemodynamic effects of insulin (300 mU·m-2·min-1) alone and during femoral artery infusion of BQ123 (an antagonist of type A endothelin receptors, 1 μmol/min). Endothelin antagonism augmented skeletal muscle responses to insulin in obese subjects through changes in both leg blood flow (LBF) and glucose extraction. Insulin-stimulated LBF was significantly increased in obese subjects only. These changes, combined with differential effects on glucose extraction, resulted in augmented insulin-stimulated leg glucose uptake in obese subjects (54.7 ± 5.7 vs. 107.4 ± 18.9 mg/min with BQ123), with no change in lean subjects (103.7 ± 11.4 vs. 88.9 ± 16.3, P = 0.04 comparing BQ123 across groups). BQ123 allowed augmented leg glucose extraction in obese subjects even in the face of NOS antagonism. These findings suggest that increased endogenous endothelin action contributes to insulin resistance in skeletal muscle of obese humans, likely through both vascular and tissue effects.

Original languageEnglish
Pages (from-to)728-734
Number of pages7
JournalDiabetes
Volume56
Issue number3
DOIs
StatePublished - Mar 2007

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Endothelins
Insulin
Leg
Skeletal Muscle
Glucose
Insulin Resistance
Endothelin A Receptors
Femoral Artery
Vasodilation
Blood Vessels
Blood Glucose
Obesity
Hemodynamics
cyclo(Trp-Asp-Pro-Val-Leu)

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Endothelin limits insulin action in obese/insulin-resistant humans. / Lteif, Amale; Vaishnava, Prashant; Baron, Alain D.; Mather, Kieren.

In: Diabetes, Vol. 56, No. 3, 03.2007, p. 728-734.

Research output: Contribution to journalArticle

Lteif, Amale ; Vaishnava, Prashant ; Baron, Alain D. ; Mather, Kieren. / Endothelin limits insulin action in obese/insulin-resistant humans. In: Diabetes. 2007 ; Vol. 56, No. 3. pp. 728-734.
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