Effect of visfatin on K(ATP) channel upregulation in colonic smooth muscle cells in diabetic colon dysmotility

The mechanisms of diabetes-related gastrointestinal dysmotility remains unclear. This study aimed to investigate the effect and mechanisms of proinflammatory adipokine visfatin (VF) in the contractile dysfunction of diabetic rat colonic smooth muscle. Twenty Sprague-Dawley rats were randomly divided into control and type 2 diabetes mellitus groups. VF levels in the serum and colonic muscle tissues were tested, the time of the bead ejection and contractility of colonic smooth muscle strips were measured, and the expression of ATP-sensitive potassium (K(ATP)) channels in the colonic muscle tissues was analyzed. In vitro, we tested VF’s effects on intracellular reactive oxygen species (ROS) levels, NF-κB’s nuclear transcription, K(ATP) channel expression, intracellular Ca(2+) concentrations, and myosin light chain (MLC) phosphorylation in colonic smooth muscle cells (CSMCs). The effects of NAC (ROS inhibitor) and BAY 11-7082 (NF-κB inhibitor) on K(ATP) expression were also tested. Diabetic rats showed elevated VF levels in serum and colonic muscle tissues, a delayed distal colon ejection response time, weakened contractility of colonic smooth muscle strips, and increased K(ATP) channel expression in colonic muscle tissues. VF significantly inhibited the contractility of colonic smooth muscle strips from normal rats. In cultured CSMCs, VF caused ROS overload, increased NF-κB nuclear transcription activity and increased expression of Kir6.1, eventually reducing intracellular Ca(2+) levels and MLC phosphorylation. NAC and BAY 11-7082 inhibited the VF–induced Kir6.1 upregulation. In conclusion, VF may cause contractile dysfunction of CSMCs by upregulating the expression of the Kir6.1 subunit of K(ATP) channels via the ROS/NF-κB pathway and interfering with Ca(2+) signaling.