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Effects of central administration of insulin or L-NMMA on rat skeletal muscle microvascular perfusion
journal contribution
posted on 2023-05-17, 03:23 authored by Bradley, EA, Willson, KJ, Derek Choi-LundbergDerek Choi-Lundberg, Michael ClarkMichael Clark, Stephen RattiganStephen RattiganAim: 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 ìg) 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 ìg) 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 ìg/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.
History
Publication title
Diabetes Obesity & MetabolismVolume
12Issue
10Pagination
900-908ISSN
1462-8902Department/School
Menzies Institute for Medical ResearchPublisher
Blackwell Publishing LtdPlace of publication
9600 Garsington Rd, Oxford, England, Oxon, Ox4 2DgRights statement
The definitive published version is available online at: http://onlinelibrary.wiley.com/Repository Status
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