Insulin resistance in mice lacking neuronal nitric oxide synthase is related to an alpha-adrenergic mechanism

Turini, P; Thalmann, S; Jayet, P-Y; Cook, S; Mathieu, C; Burcelin, R; Nicod, P; Vollenweider, P; Sartori, C; Scherrer, U (2007). Insulin resistance in mice lacking neuronal nitric oxide synthase is related to an alpha-adrenergic mechanism. Swiss medical weekly, 137(49-50), pp. 700-4. Muttenz: EMH Schweizerischer Ärzteverlag

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BACKGROUND: nitric oxide (NO) plays an important role in the regulation of cardiovascular and glucose homeostasis. Mice lacking the gene encoding the neuronal isoform of nitric oxide synthase (nNOS) are insulin-resistant, but the underlying mechanism is unknown. nNOS is expressed in skeletal muscle tissue where it may regulate glucose uptake. Alternatively, nNOS driven NO synthesis may facilitate skeletal muscle perfusion and substrate delivery. Finally, nNOS dependent NO in the central nervous system may facilitate glucose disposal by decreasing sympathetic nerve activity. METHODS: in nNOS null and control mice, we studied whole body glucose uptake and skeletal muscle blood flow during hyperinsulinaemic clamp studies in vivo and glucose uptake in skeletal muscle preparations in vitro. We also examined the effects of alpha-adrenergic blockade (phentolamine) on glucose uptake during the clamp studies. RESULTS: as expected, the glucose infusion rate during clamping was roughly 15 percent lower in nNOS null than in control mice (89 (17) vs 101 (12) [-22 to -2]). Insulin stimulation of muscle blood flow in vivo, and intrinsic muscle glucose uptake in vitro, were comparable in the two groups. Phentolamine, which had no effect in the wild-type mice, normalised the insulin sensitivity in the mice lacking the nNOS gene. CONCLUSIONS: insulin resistance in nNOS null mice was not related to defective insulin stimulation of skeletal muscle perfusion and substrate delivery or insulin signaling in the skeletal muscle cell, but to a sympathetic alpha-adrenergic mechanism.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology
UniBE Contributor:	Cook, Stéphane
ISSN:	1424-7860
ISBN:	18197485
Publisher:	EMH Schweizerischer Ärzteverlag
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:54
Last Modified:	05 Dec 2022 14:17
PubMed ID:	18197485
Web of Science ID:	000252028600003
URI:	https://boris.unibe.ch/id/eprint/23220 (FactScience: 40631)