title: Decreased microvascular vasomotion and myogenic response in rat skeletal muscle in association with acute insulin resistance.
abstract: In addition to increased glucose uptake, insulin action is associated with increased total and microvascular blood flow, and vasomotion in skeletal muscle. The aim of this study was to determine the effect of acute insulin resistance caused by the peripheral vasoconstrictor alpha-methylserotonin (alphaMT) on microvascular vasomotion in muscle. Heart rate (HR), mean arterial pressure (MAP), femoral blood flow (FBF), whole body glucose infusion (GIR) and hindleg glucose uptake (HGU) were determined during control and hyperinsulinaemic euglycaemic clamp conditions in anaesthetized rats receiving alphaMT infusion. Changes in muscle microvascular perfusion were measured by laser Doppler flowmetry (LDF) and vasomotion was assessed by applying wavelet analysis to the LDF signal. Insulin increased GIR and HGU. Five frequency bands corresponding to cardiac, respiratory, myogenic, neurogenic and endothelial activities were detected in the LDF signal. Insulin infusion alone increased FBF (1.18 +/- 0.10 to 1.78 +/- 0.12 ml min(-1), P < 0.05), LDF signal strength (by 16% compared to baseline) and the relative amplitude of the myogenic component of vasomotion (0.89 +/- 0.09 to 1.18 +/- 0.06, P < 0.05). When infused alone alphaMT decreased LDF signal strength and the myogenic component of vasomotion by 23% and 27% respectively compared to baseline, but did not affect HGU or FBF. Infusion of alphaMT during the insulin clamp decreased the stimulatory effects of insulin on GIR, HGU, FBF and LDF signal and blocked the myogenic component of vasomotion. These data suggest that insulin action to recruit microvascular flow may in part involve action on the vascular smooth muscle to increase vasomotion in skeletal muscle to thereby enhance perfusion and glucose uptake. These processes are impaired with this model of alphaMT-induced acute insulin resistance.
authors.affiliation: Menzies Research Institute, University of Tasmania, Hobart 7001, Australia. J.Newman@menzies.utas.edu.au
authors.forename: John M B
authors.initials: JM
authors.lastname: Newman
authors.forename: Renee M
authors.initials: RM
authors.lastname: Dwyer
authors.forename: Philippe
authors.initials: P
authors.lastname: St-Pierre
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Richards
authors.forename: Michael G
authors.initials: MG
authors.lastname: Clark
authors.forename: Stephen
authors.initials: S
authors.lastname: Rattigan
mesh_terms: D000208:Acute Disease; D000818:Animals; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D015309:Glucose Clamp Technique; D006339:Heart Rate; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D007333:Insulin Resistance; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives; D013997:Time Factors; D014463:Ultrasonography; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014662:Vasoconstrictor Agents; C042390:alpha-methylserotonin; D012701:Serotonin