Effect of visfatin on KATP channel upregulation in colonic smooth muscle cells in diabetic colon dysmotility

Abstract

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 ATPsensitive 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.

The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis

“…VAT and SAT tissues express comparable levels of visfatin [ 69 ]. Secreted visfatin was shown to exert inflammatory and profibrotic activities [ 70 , 71 , 72 ]. Notably, visfatin up-regulated fibrotic proteins in adipocytes [ 73 ].…”

“…Visfatin is the extracellular form of nicotinamide phosphoribosyltransferase (NAMPT). Visfatin secreted from WAT, elevated in the serum of individuals with T2D, metabolic syndrome or obesity, was shown to exert inflammatory and profibrotic activities [ 70 , 71 , 72 ]. Visfatin is suggested so contribute to adipose tissue fibrosis being related to insulin resistance, liver steatosis and metabolic diseases [ 74 ].…”