N. Ueno, A. Inui, A. Asakawa
May 15, 2002
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Influential Citations
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Journal
Diabetologia
Abstract
AbstractAims/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). Sixty-nine 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). Results. Mosapride lowered fasting blood glucose and fructosamine concentrations (p<0.05) (first study). It significantly increased the number of (Mosapride 3323±518 vs 4481±786 [p<0.05], Control 4227±761 vs 3275±554 per 300 µl erythrocytes) and the tyrosine autophosphorylation (Mosapride 3178±444 vs 4043±651 [p<0.05], Control 3721±729 vs 3013±511 insulin receptor unit) of insulin receptors, as well as glucose utilisation (Mosapride 4.92±0.53 vs 5.88±0.72 [p<0.05], Control 4.74±0.65 vs 4.70±0.31 mg/kg·min). Mosapride treatment for 8 weeks significantly reduced fasting glucose (9.91±0.34 vs 8.51±0.34 mmol/l, p<0.05), insulin (53.2±4.62 vs 40.8±5.52 pmol/l, p<0.05) and HbA1c (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.