Acute impairment of insulin-mediated capillary recruitment and glucose uptake in rat skeletal muscle in vivo by TNF-alpha
Youd, JM and Rattigan, S and Clark, MG, Acute impairment of insulin-mediated capillary recruitment and glucose uptake in rat skeletal muscle in vivo by TNF-alpha, Diabetes, 49, (11) pp. 1904-1909. ISSN 0012-1797 (2000) [Refereed Article]
The vascular actions of insulin may contribute to the increase in glucose uptake by skeletal muscle. We have recently shown that when capillary recruitment by insulin is blocked in vivo, an acute state of insulin resistance is induced. Another agent that may have vascular effects is the inflammatory cytokine tumor necrosis factor-α (TNF-α), which has been reported to play an important role in the insulin resistance of obesity, type 2 diabetes, and sepsis in both animals and humans. Thus, in the present study, we have investigated the effect of an intravenous 3-h TNF treatment (0.5 υg. h-1 · kg-1) in control and euglycemic-hyperinsulinemicclamped (10 mU · min-1 · kg-1 for 2 h) anesthetized rats. Hind-leg glucose uptake, muscle uptake of 2-deoxyglucose (2-DG), femoral blood flow (FBF), vascular resistance (VR), and capillary recruitment as measured by metabolism of infused 1-methylxanthine (1-MX) were assessed. Insulin alone caused a significant (P < 0.05) increase in FBF (1.7-fold) and capillary recruitment (2.5-fold), with a significant decrease in VR. In addition, hind-leg glucose uptake was increased (fourfold), as was 2-DG uptake in the soleus and plantaris muscles. TNF completely prevented the insulin-mediated changes in FBF, VR, and capillary recruitment and significantly reduced (P < 0.05) the insulin-mediated increase in total hind-leg glucose uptake (by 61%) and muscle 2-DG uptake (by at least 50%). TNF alone had no significant effect on any of these variables. It is concluded that acute administration in vivo of TNF completely blocks the hemodynamic actions of insulin on rat skeletal muscle vasculature and blocks approximately half of the glucose uptake by muscle. It remains to be determined whether these two effects are interdependent.