| 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). 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 microl 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 x 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 HbA(1c) (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. |
| Authors | N Ueno, A Inui, A Asakawa, F Takao, Y Komatsu, K Kotani, R Nishimura, M Kasuga
(Affiliation: Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.)
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| Journal | Diabetologia
(Diabetologia)
Vol. 45
Issue 6
Pg. 792-7
(Jun 2002)
ISSN: 0012-186X Germany |
| PMID | 12107722
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Benzamides
- Blood Glucose
- DNA Primers
- Gastrointestinal Agents
- Hemoglobin A, Glycosylated
- Hypoglycemic Agents
- Lipids
- Morpholines
- Placebos
- Receptors, Serotonin
- Serotonin Agonists
- Insulin
- mosapride
- Receptors, Serotonin, 5-HT4
- Fructosamine
|
| Topics |
- Base Sequence
- Benzamides
(therapeutic use)
- Blood Glucose
(drug effects, metabolism)
- DNA Primers
- Diabetes Mellitus, Type 2
(blood, drug therapy)
- Female
- Fructosamine
(blood)
- Gastrointestinal Agents
(therapeutic use)
- Hemoglobin A, Glycosylated
(metabolism)
- Humans
- Hypoglycemic Agents
(therapeutic use)
- Insulin
(blood)
- Lipids
(blood)
- Male
- Middle Aged
- Morpholines
(therapeutic use)
- Placebos
- Receptors, Serotonin
(drug effects, genetics, physiology)
- Receptors, Serotonin, 5-HT4
- Reverse Transcriptase Polymerase Chain Reaction
- Serotonin Agonists
(therapeutic use)
|
