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Effects of central administration of insulin or L-NMMA on rat skeletal muscle microvascular perfusion

Citation

Bradley, EA and Willson, KJ and Choi-Lundberg, D and Clark, MG and Rattigan, S, Effects of central administration of insulin or L-NMMA on rat skeletal muscle microvascular perfusion, Diabetes Obesity & Metabolism, 12, (10) pp. 900-908. ISSN 1462-8902 (2010) [Refereed Article]


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The definitive published version is available online at: http://onlinelibrary.wiley.com/

Official URL: http://onlinelibrary.wiley.com

DOI: doi:10.1111/j.1463-1326.2010.01253.x

Abstract

Aim: Intracerebroventricular (ICV) administration of a nitric oxide synthase (NOS) inhibitor to rats has been reported to raise blood pressure (BP) and cause insulin resistance, suggestive of a central effect of insulin that is NO dependent. Herein we test whether ICV insulin has peripheral haemodynamic and metabolic effects and whether peripheral effects of systemic insulin are affected by the ICV administration of the NOS inhibitor NG-methyl-L-arginine (L-NMMA). Methods: Anaesthetized rats were fitted with an ICV cannula for insulin, artificial cerebrospinal fluid (aCSF) or L-NMMA infusion. Rats receiving ICV L-NMMA (500 g) underwent systemic insulin clamp (10 mU/min/kg) or saline treatment for 70 min and were compared with animals receiving an equal amount of L-NMMA infused systemically. Results: ICV aCSF or insulin (135 mU/min/kg brain) for 70 min or systemic L-NMMA (500 g) had no effect on BP, heart rate (HR), femoral blood flow (FBF), glucose infusion rate, muscle 2-deoxyglucose uptake, microvascular perfusion or plasma insulin. However, ICV L-NMMA reduced systemic insulin-mediated increases in FBF (2.05 0.08 to 1.55 0.15 ml/min), 2-deoxyglucose uptake (17.7 0.15 to 10.0 0.03 g/g/min) and microvascular perfusion (10.5 0.5 to 6.6 1.1 mol/min) (each mean SE, p < 0.05); plasma insulin, HR and BP were unaffected. Conclusions: Central insulin administration had no effect on skeletal muscle haemodynamics or glucose metabolism. However, systemic insulin-mediated increases in limb blood flow, muscle microvascular perfusion and glucose uptake may be regulated by a central pathway that is NO dependent.

Item Details

Item Type:Refereed Article
Keywords:blood flow, intracerebroventricular, muscle glucose uptake, muscle insulin action, nitric oxide synthase
Research Division:Medical and Health Sciences
Research Group:Other Medical and Health Sciences
Research Field:Medical and Health Sciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Diabetes
Author:Bradley, EA (Miss Eloise Bradley)
Author:Willson, KJ (Mr Kaspar Willson)
Author:Choi-Lundberg, D (Dr Derek Choi-Lundberg)
Author:Clark, MG (Professor Michael Clark)
Author:Rattigan, S (Professor Stephen Rattigan)
ID Code:65271
Year Published:2010
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-10-26
Last Modified:2011-05-02
Downloads:0

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