The relationship between central serotonergic activity and insulin sensitivity in healthy volunteers

In order to determine whether central serotonin (5-HT) activity is related to sensitivity of insulin receptors, 19 healthy volunteers with normal basa l glycemia and HbAlc were studied. The relationship between prolactin respo nse to D-fenfluramine (Delta PRL) in a challenge test and metabolic clearan ce rates (MCR) of glucose during the hyperinsulinemic-euglycemic clamp tech nique was evaluated. Delta PRL had been chosen as a correlate of central 5- HT activity. Two levels of insulin concentration of approximately 70 mU/1 ( MCRsubmax) and 2000 mU/1 (MCRmax) were used in a clamp, each for a duration of 120 min. A negative correlation was found between Delta PRL and MCRsubm ax (r = -0.55, P < 0.02) and between Delta PRL and MCRmax (r = -0.51, P < 0 .03). We did not find any correlation between the prolactin response to D-f enfluramine and body weight, body mass index (BMI) or waist and hip circumf erence (WHR). The data support the hypothesis of a close connection between 5-HT activity in the brain and peripheral sensitivity to insulin. The poss ible physiological mechanisms of this connection are discussed. (C) 1999 El sevier Science Ltd. All rights reserved.