Mosapride, a 5HT-4 receptor agonist, improves insulin sensitivity and glycaemic control in patients with Type II diabetes mellitus

Abstract

Aims/hypothesis. We investigated the potential role of mosapride, a 5HT-4 receptor agonist, in glycaemic control in Type II (non-insulin-dependent) diabetic mellitus patients without autonomic neuropathy. Methods. Thirty-four inpatients with Type II diabetes mellitus were randomly assigned to receive either mosapride (5 mg orally three times a day, n=17) or a placebo (n=17) for 1 week (first study). Changes in blood glucose and insulin were determined basally as well as after intravenous glucose loading. Insulin sensitivity was evaluated during hyperinsulinaemic-normoglycaemic-clamp studies and by measuring the number of and the autophosphorylation of insulin receptors on the erythrocytes of patients (n=9). Sixtynine outpatients with Type II diabetes were similarly treated with mosapride or a placebo for 8 weeks (second study). Finally, tissue-specific expression of 5HT-4 receptors was examined by reverse transcriptase-polymerase chain reaction (RT-PCR (8.61±0.20 vs 7.67±0.19%, p<0.01) concentrations (second study). The RT-PCR analysis demonstrated specific expression of 5HT-4 receptors in the muscle, but not in the liver or fat tissues. Conclusions/interpretation. Mosapride could improve insulin action at muscle and glycaemic control in Type II diabetic patients. [Diabetologia (2002) 45:792-797]

Mosapride Citrate Increases Postprandial Glucagon-Like Peptide-1, Insulin, and Gene Expression of Sweet Taste Receptors

“…In the current study, the expression of sweet taste receptors in the duodenum, proximal jejunum, and mid-jejunum-very upper intestine-was increased by the administration of mosapride citrate but not by domperidone, which is also a prokinetic agent. This result corresponds to the observation that only mosapride citrate has the property of enhancing insulin sensitivity and glucose utilization in muscle, unlike domperidone and metoclopramide [4,42], whereas domperidone is effective for diabetic gastropathy as is mosapride citrate [5,43,44]. This enhancement of insulin sensitivity in muscle may be caused by GLP-1 which was increased by the administration of mosapride citrate.…”

“…This drug has been widely used in Japan, and its significance was again highlighted when it was found to be effective against functional gastrointestinal disorders in a large, randomized clinical trial [3]. The drug has pharmacological properties of reducing hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes [4,5]. Ueno et al [4] demonstrated that mosapride citrate intake increases sugar utilization through enhanced insulin sensitivity in muscle, and Nam et al [6] showed that the drug increased the mobilization of glucose transporters from intracellular pools in muscle; however, the causative mechanisms are unclear.…”

Mosapride citrate, a 5-HT₄ receptor agonist, increased the plasma active and total glucagon-like peptide-1 levels in non-diabetic men

“…Ueno et al reported that the administration of mosapride citrate for one week significantly improved the glucose responses as evaluated using an intravenous glucose test [12]. They also reported that the administration of mosapride citrate significantly increased the number of and the tyrosine autophosphorylation of insulin receptors as well as the No significant differences in the time profiles and the AUCs for the plasma total GIP levels were observed between the two groups ( Fig.…”

“…Mosapride has no dopamine D 2 receptor antagonist activity, unlike other gastrokinetic agents such as metoclopramide [11]. Mosapride citrate reportedly improves glycemic control in patients with type 2 diabetes [12] and in patients with gastropathy arising from diabetes [13]. By contrast, cisapride, which is another selective agonist of the 5-HT 4 receptor but is presently prohibited because of its effect on the QT interval, has no effect on glycemic control [14, MA, USA) at SRL, Inc. (Tokyo, Japan).…”

Gastrointestinal Motility Disorders: An Update

“…In one study, mosapride improved gastric motility in diabetic gastropathy and also improved glycemic control with a corresponding decrease in HgA1C [126,127] .…”