Tianeptine Enhances Insulin Secretion Throughout the Oral Glucose Tolerance Test

Drugs that inhibit the uptake of serotonin at the synaptic level, such as doxepin, are able to counteract hyperinsulism-induced hypoglycemia. Thus, we postulated that tianeptine, a drug which facilitates the uptake of serotonin at both synaptic and platelet levels, might display an antidiabetogenic effect. We investigated the oral glucose tolerance test (OGTT) + placebo in 38 normal humans. A second OGTT + tianeptine was performed 2 weeks later in the same subjects. We found that tianeptine potentiated a significant and sustained increase of insulin registered during the OGTT, further evidenced by a decrease in plasma glucose. Significant increases of the plasma noradrenaline (NA)/adrenaline (Ad) ratio paralleled insulin rises. Additionally, the positive correlation observed between the NA/Ad plasma and insulin levels is consistent with the well-known fact that insulin crosses the blood-brain barrier and excites the central nervous system (CNS)-noradrenergic neurons responsible for peripheral sympathetic nerve activity. Furthermore, significant reductions of both circulating serotonin (plasma serotonin plus platelet serotonin) registered throughout the tianeptine + glucose challenge. This observation supports the postulation that the drug interferes with the normal peripheral parasympathetic activity demonstrated throughout the OGTT. This hypoparasympathetic effect triggered by the drug is responsible for the hyposecretion of serotonin from the enterochromaffin cells. In conclusion, tianeptine potentiates the insulinogenic effect of OGTT throughout both CNS and peripheral mechanisms. Both effects depend on the drug’s interference at Tianeptine Enhances Insulin Secretion Throughout the Oral Glucose Tolerance