Serotonin-mediated acute insulin resistance in the perfused rat hindlimb but not in incubated muscle: a role for the vascular system.

Abstract:

:We have recently shown that the vasoconstrictor serotonin (5-HT) inhibits oxygen uptake in perfused hindlimb possibly due to vascular shunting. Thus in the present study the effect of 5-HT on insulin-mediated glucose uptake was assessed. Rat hindlimbs were perfused at constant flow with medium containing 8.3 mM glucose and a tracer amount of 2-deoxy-D-[1-3]glucose (2DG) with and without 10 microM 5-HT, 15 nM insulin and a combination of the two. 5-HT inhibited insulin-mediated stimulation 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) to 80% (extensor digitorum longus). The effects of 5-HT on insulin-mediated glucose uptake were partially reversed by vasodilation with carbachol. In contrast to the results for the hindlimb, 10 microM 5-HT had no significant effect on either basal glucose uptake or the stimulation of glucose uptake mediated by 15 nM insulin by isolated incubated soleus or extensor digitorum longus muscles. It is concluded that 5-HT impairs insulin-mediated glucose uptake in the perfused rat hindlimb that may derive from vascular shunting not apparent when muscles are incubated with 5-HT in vitro. These findings may have implications for the link between hypertension and diabetes.

journal_name

Life Sci

journal_title

Life sciences

authors

Rattigan S,Dora KA,Colquhoun EQ,Clark MG

doi

10.1016/0024-3205(93)90563-i

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

1545-55

issue

20

eissn

0024-3205

issn

1879-0631

pii

0024-3205(93)90563-I

journal_volume

53

pub_type

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