Insulin increases hindlimb blood flow more in fed than in fasted Wistar rats

University of Manchester (2010) Proc Physiol Soc 19, C76

Oral Communications: Insulin increases hindlimb blood flow more in fed than in fasted Wistar rats

A. E. Stride1, C. J. Ray1, R. Macdonald3, A. J. Wagenmakers2, S. M. Poucher3, J. M. Marshall1

1. School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom. 2. School of Sport and Exercise Science, University of Birmingham, Birmingham, United Kingdom. 3. CVGI Discovery, AstraZeneca Pharmaceuticals, Macclesfield, United Kingdom.

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Insulin increases skeletal muscle blood flow suggesting it can mediate glucose disposal via increased peripheral delivery (1). The resulting increase in capillary blood flow may also facilitate translocation of insulin into the interstitial fluid enabling greater access to insulin receptors (2). We have investigated whether the vasodilator effects of insulin are different in the fed and fasted states. In terminally anaesthetized (Alfaxan 12mg.kg-1.hr-1 I.V.) male Wistar rats (222±14g; mean±SEM) arterial blood pressure (ABP) and femoral blood flow (FBF) were recorded. Femoral vascular conductance (FVC=FBF/ABP) was calculated. Responses to hyperinsulinaemic-euglycaemic clamp (30mU.min-1.kg-1 for 120 mins) were measured in fed (food and water ad libitum; n=7) and fasted (food withdrawn 16 hours before experimentation, water ad libitum; n=8) rats. Glucose infusion rate was increased at a rate continuously adjusted to maintain blood glucose at basal levels. Comparisons were made using factorial ANOVA, *P<0.05. Baseline blood glucose (6.4±0.2 vs 3.5±0.2 mmol.L-1*; fed vs. fasted) and glucose infusion rate required to maintain basal blood glucose levels was significantly higher in fed animals (38±3 vs 23±2 mg.kg-1.min-1*). ABP was not affected so changes in FBF directly reflect vasodilator responses. Baseline FBF was greater in fasted animals (1.07±0.14 vs 1.59±0.23 ml.min-1; P=0.07). In fed animals, the hyperinsulinaemic-euglycaemic clamp increased FBF to 1.54±0.20 ml.min-1* with maximal dilatation at 60 mins, but in fasted animals the FBF increased only to 1.78±0.30 ml.min-1 with maximal dilatation at 50 mins. Analysis of integrated FBF showed a significant difference between fed and fasted animals (1389±502 vs -779±785 mls*). Despite attempts to control blood glucose in fed animals, blood glucose fell at the start of the hyperinsulinaemic-euglycaemic clamp. Since acute hypoglycaemia releases catecholamines (3), in a further group of fed animals hyperinsulinaemic-euglycaemic clamp was repeated after selective β2-adrenoceptor antagonism with ICI 551 118 (0.5mg.kg-1 I.A.). ICI 551 118 had no effect on the increase in FBF during hyperinsulinaemic-euglycaemic clamp. These results suggest that in fasted animals baseline FBF is higher but the vasodilator response to insulin is smaller than in fed animals.



Where applicable, experiments conform with Society ethical requirements.

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