Beneficial effects of sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, supplemented with pioglitazone on diabetic model mice.
OBJECTIVE
Feeding behavior control and dietetics with consequent weight reduction can be the most efficacious and fundamental methods to normalize fasting blood glucose. However, pioglitazone treatment has been found to incrementally increase body weight. In this study, we investigated whether the combined application of a 5-HT(2A) receptor antagonist, sarpogrelate, with pioglitazone can provide a clinical benefit.


METHODS
Diabetic male KK-A(y) mice were randomly assigned to four groups: those receiving 10 mg/kg/day pioglitazone treatment for 30 days (pioglitazone group, n = 7), those receiving 30 mg/kg/day sarpogrelate treatment for 30 days (sarpogrelate group, n = 7), those receiving both agents for 30 days (pioglitazone + sarpogrelate group, n = 7) and those receiving no treatment (control group, n = 7).


RESULTS
Feed intake was lower in the pioglitazone + sarpogrelate group than in the pioglitazone group. Water intake was also significantly lower in the pioglitazone, sarpogrelate and pioglitazone + sarpogrelate groups than in the control group. Combined application (pioglitazone + sarpogrelate) resulted in a 176% increase in leptin concentration compared with vehicle control. Body weight was significantly higher in the pioglitazone group, and there was a trend toward a smaller increment in body weight in the pioglitazone + sarpogrelate group. Mean values, calculated by multiplying insulin concentration and nonfasting glucose concentration, were significantly lower in the pioglitazone + sarpogrelate group than in the control group.


CONCLUSIONS
These results suggest that the combined application of sarpogrelate with pioglitazone provides therapeutic benefits not only in preventing adverse effects but also in the treatment of diabetes.
Iizuka
Kenji
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Toubetsu, Hokkaido, Japan. kiizuka@hoku-iryo-u.ac.jp
Hamaue
Naoya
N
Machida
Takuji
T
Hirafuji
Masahiko
M
Tsuji
Masahiro
M
D050153:Abdominal Fat / Q000033:anatomy & histology / Q000187:drug effects; D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002452:Cell Count; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D000077205:Pioglitazone; D058830:Serotonin 5-HT2 Receptor Antagonists; D013386:Succinates / Q000008:administration & dosage / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000008:administration & dosage
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D008055:Lipids; D058830:Serotonin 5-HT2 Receptor Antagonists; D013386:Succinates; D045162:Thiazolidinediones; C064294:sarpogrelate; D000077205:Pioglitazone