Aims/hypothesis. Insulin has nitric-oxide-dependent vasodilatory effects in muscle, including capillary recruitment, that enhance access for itself and glucose. However, nitric-oxide-dependent vasodilators other than methacholine do not enhance insulin action. Our hypothesis is that methacholine, unlike bradykinin, enhances insulin-mediated glucose uptake in muscle by augmenting capillary recruitment. Methods. Local infusion of either methacholine or bradykinin into one leg of the anaesthetised rat was made during physiological insulin (3 mU·kg-1min-1) infusion under euglycaemic conditions and without affecting systemic blood pressure. Whole-body glucose infusion was determined, as was femoral blood flow, 2-deoxyglucose uptake into calf muscles and the metabolism of infused 1-methylxanthine, a measure of capillary recruitment for each leg. Results. Methacholine alone (0.3 μmol·l-1) increased femoral arterial blood flow, increased capillary recruitment but had no effect on 2-deoxyglucose uptake of the test leg relative to the contra-lateral control leg. Insulin alone (systemically) required a glucose infusion rate of 8.7 mg·kg-1min -1 to maintain euglycaemia, increased 2-deoxyglucose uptake and capillary recruitment, but was without effect on femoral blood flow in either leg. Local methacholine with systemic insulin infusion increased femoral blood flow, 2-deoxyglucose uptake and capillary recruitment in the test leg only. Bradykinin (0.07 μmol·l-1), alone or with insulin, administered in a manner that increased femoral blood flow similarly to methacholine, did not affect 2-deoxyglucose uptake or capillary recruitment. Conclusions/interpretation. Methacholine but not bradykinin enhances insulin-mediated muscle glucose uptake in vivo. We conclude that methacholine acts at specific sites in the vasculature of muscle to stimulate capillary recruitment and thereby enhance insulin access. © Springer-Verlag 2004.

Item Type:	Refereed Article
Research Division:	Medical and Health Sciences
Research Group:	Clinical Sciences
Research Field:	Endocrinology
Objective Division:	Health
Objective Group:	Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:	Diabetes
Author:	Mahajan, H (Dr Hema Mahajan)
Author:	Richards, SM (Dr Stephen Richards)
Author:	Rattigan, S (Professor Stephen Rattigan)
Author:	Clark, MG (Professor Michael Clark)
ID Code:	31444
Year Published:	2004
Web of Science® Times Cited:	15
Deposited By:	Biochemistry
Deposited On:	2004-08-01
Last Modified:	2005-03-21
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