SEROTONIN-MEDIATED ACUTE INSULIN-RESISTANCE IN THE PERFUSED RAT HINDLIMB BUT NOT IN INCUBATED MUSCLE - A ROLE FOR THE VASCULAR SYSTEM

We have recently shown that the vasoconstrictor serotonin (5-HT) inhib its oxygen uptake in perfused hindlimb possibly due to vascular shunti ng. Thus in the present study the effect of 5-HT on insulin-mediated g lucose uptake was assessed. Rat hindlimbs were perfused at constant fl ow with medium containing 8.3 mM glucose and a tracer amount of 2-deox y-D-[1-H-3]glucose (2DG) with and without 10 muM 5-HT, 15 nM insulin a nd a combination of the two. 5-HT inhibited insulin-mediated stimulati on of glucose uptake by 30.4% when added after insulin and 34.4% when added before insulin In addition, 5-HT inhibited insulin-mediated 2DG uptake by perfused muscles with inhibition ranging from 32% (soleus) t o 80% (extensor digitorum longus). The effects of 5-HT on insulin-medi ated glucose uptake were partially reversed by vasodilation with carba chol. In contrast to the results for the hindlimb, 10 muM 5-HT had no significant effect on either basal glucose uptake or the stimulation o f glucose uptake mediated by 15 nM insulin by isolated incubated soleu s or extensor digitorum longus muscles. It is concluded that 5-HT impa irs insulin-mediated glucose uptake in the perfused rat hindlimb that may derive from vascular shunting not apparent when muscles are incuba ted with 5-HT in vitro. These findings may have implications for the l ink between hypertension and diabetes.