Abstract
BACKGROUND:Recent research suggests that administration of serotonin or 5-hydroxytryptamine (5-HT) its precursors or agonists of ttheir receptors can modulate glycemia in rodents; being 5 HT2A the main receptors involved in glycemia reduction. Therefore, we decided to investigate the effect of TR3370 a quipazine analogue, over glycemia.
METHODS: Oral glucose tolerance tests (OGTT, 2 g/kg) were performed in healthy and fasted male Wistar rats in order to assess TR3370 effect using 5.7, 7.5, 10, 13.3, 14.3, 17.7 and 30 mg/Kg doses. Once the effect of TR3370 over glycemia was determined we decided to stay on 14.3 mg/Kg dose, which was used to pharmacologically assess the role of 5-HT2 in the anti-hyperglycemic effect of TR3370 using OGTT, in animals previously trated with pelanserine (5-HT2 antagonist, 2.5 mg/kg, i.p.). Later, insulin determining OGTT were performed (insulin (Rat) ELISA; ALPCO Immunoassays) in normal rats in order to determine if a TR3370-triggered an increase in insulin release. There experiments were compared whit a group receiving glibenclamide, an antidiabetic antidiabetic releasing insulin insulin. Finally, OGTT were performed in streptozotocin (60 mg/Kg, i.p.) hyperglycemic rats to assess the role of insuline in the anti-hyperglycemic effect of TR3370.
RESULTS AND CONCLUSION:The 14.3 mg/Kg dose of TR3370 controlled postprandial glucose levels during an oral glucose tolerance test (OGTT, 2 g/kg) in healthy and sreptozotocin (STZ, 60 mg/kg) hyperglycemic rats. In OGTT, Pelanserin, a 5-HT2 antagonist, blocked the effect of TR3370 suggesting that 5- HT2 receptors are involved in the anihiperglycemict effect of the TR3370. When determining insulin release, we observed an increase in plasmatic insulin in rats treated with 14.3 mg/Kg of TR3370, compared with controls but less than glibenclamide. In the diabetic rats model we found that the antihyperglycemic effect of TR3370 was diminished which suggest that there could be another mechanism through TR3370 is acting. These present results suggest that TR3370 have a potential therapeutic use in pathologies such as diabetes type 2 and metabolic syndrome.
