P-561: Bradykinin-induced (BK) improvement in insulin sensitivity: A role for the potassium (K+) channel

We and others have shown previously that BK is involved in the glucose metabolism. The aim of this study was to evaluate whether this BK effect occurs through the activation of K+ channels (EDHF, endothelium derived hyper-polarization factor). The insulin sensitivity (IS) of normotensive Wistar rats (NWR) was determined in a euglicemic hyperinsulinemic clamp in the absence or in presence of 3 K+ channel blockers (glibenclamide, tetraethylammonium and 4-aminopyridine, 4AP) or openers (cromakalin, nicorandil and pinacidil, PINA). In the second set of experiments IS of NWR was determined during infusion of the BK-B2 receptor blocker (HOE-140) before and after the K+ channel opener PINA, while the IS of NWR during the administration of the K+channel blocker 4AP was evaluated before and after BK infusion. Results: In NWR, IS was reduced by all K+ channel blockers while all openers improve it. As previously shown HOE-140 reduced the IS of NWR that was partially restored toward control levels by PINA. On the other hand BK also reversed the deterioration of IS induced by 4-AP in NWR. Conclusion: K+ channels are involved in the glucose uptake by the cells and at least in part BK exert its effects on glucose metabolism through this mechanism.