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Sumatriptan, a serotonin 5HT1B receptor agonist, acutely reduces insulin secretion and sensitivity and glucose effectiveness in overweight humans: A double-blinded placebo-controlled cross-over trial.

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Hussein Ismail, Mouhamad 
Josipovic, Masa 
Kennet, Jane 
Galderisi, Alfonso 


AIM: Evidence from mouse models suggests that brain serotonergic pathways control blood glucose. We hypothesized that sumatriptan (5HT1B -receptor agonist) would alter glucose homeostasis in humans. MATERIALS AND METHODS: We conducted a two-visit random-order double-blinded placebo-controlled cross-over trial in 10 overweight adults that were otherwise healthy. Participants received sumatriptan (single dose, 100 mg) or placebo before undergoing a 60-min intravenous glucose tolerance test, followed by a 120-min hyperinsulinaemic euglycaemic clamp. RESULTS: Glucose excursion was greater during intravenous glucose tolerance test with sumatriptan compared with placebo [iAUC0-60 min 316 (268-333) vs. 251 (197-319) min/mmol/L p = .047]. This was probably explained by a combination of reduced circulating insulin levels [iAUC0-10 min 1626 (1103-2733) vs. 2336 (1702-3269) min/pmol/L, p = .005], reduced insulin sensitivity [M/I-value 2.11 (1.15, 4.05) vs. 3.03 (1.14, 4.90) mg/kg/min per pmol/L, p = .010] and glucose effectiveness [SG 0.17 (0.12, 0.21) vs. 0.22 (0.18, 0.65)/min, p = .027]. CONCLUSIONS: 5HT1B receptors have a glucoregulatory role in humans, probably acting on insulin secretion, insulin sensitivity and glucose effectiveness.


Funder: Diabetes Research and Wellness Foundation; doi:


beta cell function, drug mechanism, effectiveness, glycaemic control, insulin secretion, randomised trial, Adult, Animals, Mice, Humans, Glucose, Overweight, Insulin Secretion, Insulin Resistance, Sumatriptan, Serotonin, Cross-Over Studies, Insulin, Blood Glucose, Double-Blind Method

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Diabetes Research and Wellness Foundation (pump priming award to RG), supported by the NIHR Cambridge Biomedical Research Centre and carried out in the NIHR Cambridge Clinical Research Facility/ Translational Research Facility (TRF). The University of Cambridge has received salary support for MLE through the National Health Service in the East of England through the Clinical Academic Reserve. RG was supported by an NIHR Academic Clinical Fellowship. MJ was supported by a Gates Cambridge Trust PhD scholarship. AG is supported by the Juvenile Diabetes Research Foundation.