The effect of mosapride (5HT-4 receptor agonist) on insulin sensitivity and GLUT4 translocation

Abstract

Aims We investigated the effect of mosapride, 5HT-4 (5-hydroxytryptamine) agonist, on blood glucose level and insulin sensitivity in subjects with impaired glucose tolerance (IGT) and conducted an in vitro study to evaluate the action mechanism. Methods Thirty IGT patients were randomly assigned to receive either mosapride or placebo for 2 weeks. Biochemical profiles and insulin sensitivity index from euglycemic hyperinsulinemic clamp test were assessed before and after treatment. In cultured myotubes from human skeletal muscle cells, insulin- and mosapride-induced GLUT4 translocation and tyrosine phosphorylation of IRS-1 were determined. Results After 2 weeks of treatment with mosapride, glucose disposal rates were significantly increased up to those of control (mosapride 5.47 ± 1.72 vs 7.06 ± 2.13, P = 0.004, placebo 5.42 ± 1.85 vs 5.23 ± 1.53 mg kg −1 min −1). Fasting plasma glucose (FPG) and insulin levels were decreased. Mosapride increased the contents of GLUT4 in plasma membrane representing the increased recruitment of glucose transporters from intracellular pool. While insulin treatment on human skeletal muscle cell resulted in an increased tyrosine phosphorylation of IRS-1, mosapride did not have any effect. Conclusions Mosapride is effective in decreasing FPG without stimulating insulin secretion in IGT subjects, possibly by inducing GLUT4 translocation in skeletal muscles.