Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

M. A. Vincent, E. J. Barrett, Jonathan Lindner, M. G. Clark, S. Rattigan

Research output: Contribution to journalArticle

221 Citations (Scopus)

Abstract

We examined the effects of inhibiting nitric oxide synthase with Nω-nitro-L-arginine-methyl ester (L-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU·min-1·kg-1) significantly increased hindlimb total blood flow (0.69 ± 0.02 to 1.22 ± 0.11 ml/min, P <0.05), glucose uptake (0.27 ± 0.05 to 0.95 ± 0.08 μmol/min, P <0.05), 1-MX uptake (5.0 ± 0.5 to 8.5 ± 1.0 nmol/min, P <0.05), and skeletal muscle microvascular volume measured by CEU (10.0 ± 1.6 to 15.0 ± 1.2 video intensity units, P <0.05). Addition of L-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% (P <0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number1 48-1
StatePublished - Jul 1 2003
Externally publishedYes

Fingerprint

Muscle
Insulin
Glucose
Muscles
Hindlimb
Ultrasonics
NG-Nitroarginine Methyl Ester
Metabolism
Skeletal Muscle
Blood
Extremities
Arginine
Hyperinsulinism
Femoral Artery
Nitric Oxide Synthase
Rats
Esters
Nitric Oxide
Animals
Perfusion

Keywords

  • Capillary recruitment
  • Muscle blood flow
  • Nitric oxide
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin. / Vincent, M. A.; Barrett, E. J.; Lindner, Jonathan; Clark, M. G.; Rattigan, S.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 285, No. 1 48-1, 01.07.2003.

Research output: Contribution to journalArticle

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