Mosapride, a 5HT-4 receptor agonist, improves insulin sensitivity and glycaemic control in patients with Type II diabetes mellitus.
OBJECTIVE
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
Mosapride could improve insulin action at muscle and glycaemic control in Type II diabetic patients.
Ueno
N
N
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.
Inui
A
A
Asakawa
A
A
Takao
F
F
Komatsu
Y
Y
Kotani
K
K
Nishimura
R
R
Kasuga
M
M
D001483:Base Sequence; D001549:Benzamides / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D019270:Fructosamine / Q000097:blood; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D010919:Placebos; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D044422:Receptors, Serotonin, 5-HT4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*
D001549:Benzamides; D001786:Blood Glucose; D017931:DNA Primers; D019270:Fructosamine; D005765:Gastrointestinal Agents; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D009025:Morpholines; D010919:Placebos; D011985:Receptors, Serotonin; D044422:Receptors, Serotonin, 5-HT4; D017366:Serotonin Receptor Agonists; C062720:mosapride