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

Psychoneuroendocrinology. 1999 Nov;24(8):785-97. doi: 10.1016/s0306-4530(99)00026-8.


In order to determine whether central serotonin (5-HT) activity is related to sensitivity of insulin receptors, 19 healthy volunteers with normal basal glycemia and HbAlc were studied. The relationship between prolactin response to D-fenfluramine (delta PRL) in a challenge test and metabolic clearance rates (MCR) of glucose during the hyperinsulinemic-euglycemic clamp technique was evaluated. delta PRL had been chosen as a correlate of central 5-HT activity. Two levels of insulin concentration of approximately 70 mU/l (MCRsubmax) and 2000 mU/l (MCRmax) were used in a clamp, each for a duration of 120 min. A negative correlation was found between delta PRL and MCRsubmax (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-fenfluramine and body weight, body mass index (BMI) or waist and hip circumference (WHR). The data support the hypothesis of a close connection between 5-HT activity in the brain and peripheral sensitivity to insulin. The possible physiological mechanisms of this connection are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Body Constitution
  • Body Mass Index
  • Brain / physiology*
  • Fenfluramine
  • Glucose Clamp Technique
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Insulin Resistance / physiology
  • Male
  • Prolactin / blood
  • Receptor, Insulin / physiology*
  • Serotonin / physiology*
  • Serotonin Agents


  • Blood Glucose
  • Glycated Hemoglobin A
  • Serotonin Agents
  • Fenfluramine
  • Serotonin
  • Prolactin
  • Receptor, Insulin