Effect of sarpogrelate hydrochloride, a 5-HT2 blocker, on insulin resistance in Otsuka Long-Evans Tokushima fatty rats (OLETF rats), a type 2 diabetic rat model.
5-hydroxytryptamine (5-HT) is closely related to pathogenesis of angiopathy in type 2 diabetes. Acute and chronic effects of sarpogrelate hydrochloride (sarpogrelate), a 5-HT2 blocker, on glucose tolerance and insulin resistance were examined. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes, were randomly assigned to 2 groups; those with 30 mg/kg BW/d sarpogrelate treatment of 4 weeks (HTB group) and without (control group). The glucose infusion rate was significantly increased in the HTB group compared with the control group. The blood glucose levels after oral glucose tolerance test and levels of plasma insulin and lipids were significantly lower in the HTB group than in the control group. To investigate mechanism of the improvement by sarpogrelate, acute effect of 5-HT and its blocking effect by sarpogrelate on blood levels of glucose were examined in 25-week-old Sprague-Dawley rats. Blood glucose levels were significantly increased by administration of 5-HT. This increase was reversed by pretreatment of sarpogrelate. A plasma adrenaline level also rose significantly by injection of the 5-HT and was prevented by pretreatment of sarpogrelate. These results indicate that sarpogrelate improves insulin resistance in type 2 diabetic rats.
Takishita
Eiko
E
Department of Nutrition, School of Medicine, Tokushima University, Tokushima City, Japan.
Takahashi
Akira
A
Harada
Nagakatsu
N
Yamato
Masaki
M
Yoshizumi
Masanori
M
Nakaya
Yutaka
Y
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004195:Disease Models, Animal; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D020334:Rats, Inbred OLETF; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D007328:Insulin; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate