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Antihiperglycemic Effect of 5‐HT2 Receptor Stimulation Induced by indorenate, a serotonin analog
Author(s) -
Hong Enrique,
Lourdes Medina Juana María,
SilvaArzave Abigail
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1272.9
Subject(s) - stimulation , endocrinology , medicine , agonist , receptor , serotonin , 5 ht receptor , antagonist , metformin , 5 ht2 receptor , receptor antagonist , diabetes mellitus , oral administration , insulin , chemistry , pharmacology
The role of 5‐Hydroxytryptamine in the regulation of glycemia has been a controversial item for some time, however, there are recent findings suggesting that 5‐HT1A receptor stimulation increases the glycemia, while 5‐HT2 receptors do the opposite. Therefore, we decided to investigate the effect of indorenate, a central antihypertensive agent exerting this action by 5‐HT1A central receptor stimulation, but also possessing a 5‐HT2 peripheral receptor stimulation. Since less than 1 % of the oral administered dose penetrates into the CNS, most of the compound could stimulate the 5‐HT2 peripheral receptors leading to an antihyperglycemic effect. The oral dose of glucose (2g/kg) to fasted Wistar rats was followed by a hyperglycemia that was maximal one hr later, this effect was suppressed by the previous administration of an oral dose of 10 mg/kg of indorenate, however, metformin at an oral dose of 300 mg/kg only produce a slight, but significant decrease in hyperglycemia. Pelanserin, a 5‐HT2 antagonist, blocked the effect of indorenate, but WAY 100635, a 5HT‐1A agonist, did not. Indorenate also increase the glucose velocity needed to maintain blood glucose levels constant in an euglycemic insulin clamp in anesthetized Wistar rats. The present data suggest that indorenate may have a potential therapeutic usefulness in both, metabolic syndrome and in type2 diabetes. Support or Funding Information Authors are indebt to the SECITIDF for its support.