Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake

A. D. Baron, G. Brechtel-Hook, A. Johnson, J. Cronin, R. Leaming, Helmut Steinberg

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Abstract

To better define the time course of skeletal muscle glucose uptake and its modulation by changes in perfusion, we performed systemic euglycemic- hyperinsulinemic clamps (40 mU · m -2 · min -1 ) for a 90-min period in a group of lean, insulin-sensitive subjects (n = 9) on two occasions (~4 wk apart) with insulin-mediated vasodilation intact or inhibited. Insulin- mediated vasodilation was inhibited by an intrafemoral artery infusion of N(G)-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase. During the study, leg blood flow (LBF) and arteriovenous glucose difference (AVGΔ) were measured every 10 min; leg glucose uptake (LGU) was calculated as LGU = LBF x AVGΔ. The systemic insulin infusion caused a time- dependent increase in LBF from 0.194 ± 0.024 to 0.349 ± 0.046 l/min (P < 0.01). The intrafemoral artery infusion of L-NMMA completely inhibited this increase in LBF. AVGΔ, LGU, and whole body glucose disposal rates increased in a time-dependent manner in both studies. The maximum AVGΔ was lower with insulin-mediated vasodilation intact than when inhibited (25.9 ± 2.5 vs. 35.0 ± 1.6 mg/dl, P < 0.001). The time to achieve half-maximal (T( 1/4 )) AVGΔ was somewhat longer with insulin-mediated vasodilation intact compared with inhibited (35.6 ± 4.1 vs. 29.7 ± 1.6 min, P < 0.01). Maximal LGU was 93.9 ± 26.8 and 57.2 ± 11.6 mg/min (P < 0.005), and the T( 1/4 ) LGU was 50.2 ± 16.0 and 36.3 ± 8.8 min (P = 0.1) during intact and inhibited insulin- mediated vasodilation, respectively. Thus insulin-mediated vasodilation has a modest effect in slowing the time course at which insulin stimulates glucose uptake but has a marked effect in augmenting the maximal rate of insulin- stimulated glucose uptake in skeletal muscle. Impaired insulin-mediated vasodilation, as observed in patients with essential hypertension, may explain, at least in part, the insulin resistance observed in these patients.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume271
Issue number6 34-6
StatePublished - Dec 1 1996
Externally publishedYes

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Skeletal Muscle
Perfusion
Insulin
Glucose
Leg
Vasodilation
omega-N-Methylarginine
Arteries
Glucose Clamp Technique
Nitric Oxide Synthase
Arginine
Insulin Resistance

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake. / Baron, A. D.; Brechtel-Hook, G.; Johnson, A.; Cronin, J.; Leaming, R.; Steinberg, Helmut.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 271, No. 6 34-6, 01.12.1996.

Research output: Contribution to journalArticle

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AU - Cronin, J.

AU - Leaming, R.

AU - Steinberg, Helmut

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