TY - JOUR

T1 - The effect of melatonin on incretin hormones

T2 - results from experimental and randomized clinical studies

AU - Lauritzen, Esben Stistrup

AU - Støy, Julie

AU - Bæch-Laursen, Cecilie

AU - Grarup, Niels

AU - Jessen, Niels

AU - Hansen, Torben

AU - Møller, Niels

AU - Hartmann, Bolette

AU - Holst, Jens Juul

AU - Kampmann, Ulla

N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2021

Y1 - 2021

N2 - CONTEXT: Glucose homeostasis is under circadian control through both endocrine and intracellular mechanisms with several lines of evidence suggesting that melatonin affects glucose homeostasis.OBJECTIVE: To evaluate the acute in-vivo and in-situ effects of melatonin on secretion of the incretin hormones, GLP-1 and GIP, and their impact on β-cell insulin secretion.DESIGN: A human randomized, double-blinded, placebo-controlled crossover study combined with a confirmatory in-situ study of perfused rat intestines.SETTING: Aarhus University Hospital.Methods: Fifteen healthy male participants were examined 2 x 2 times: An oral glucose tolerance test (OGTT) was performed on day one and an isoglycemic intravenous glucose infusion replicating the blood glucose profile of the OGTT day was performed on day two. These pairs of study days were repeated on treatment with melatonin and placebo, respectively. For the in-situ study, six rat intestines and four rat pancreases were perfused arterially with perfusion buffer ± melatonin. The intestines were concomitantly perfused with glucose through the luminal compartment.RESULTS: In humans, melatonin treatment resulted in reduced GIP secretion compared with placebo (ANOVA p=0.003), an effect also observed in the perfused rat intestines (ANOVA p=0.003) in which GLP-1 secretion also was impaired by arterial melatonin infusion (ANOVA p<0.001). Despite a decrease in GIP levels, the in-vivo glucose-stimulated insulin secretion was unaffected by melatonin (p=0.78).CONCLUSION: Melatonin reduced GIP secretion during an oral glucose challenge in healthy young men but did not affect insulin secretion. Reduced GIP secretion was confirmed in an in-situ model of the rat intestine.

AB - CONTEXT: Glucose homeostasis is under circadian control through both endocrine and intracellular mechanisms with several lines of evidence suggesting that melatonin affects glucose homeostasis.OBJECTIVE: To evaluate the acute in-vivo and in-situ effects of melatonin on secretion of the incretin hormones, GLP-1 and GIP, and their impact on β-cell insulin secretion.DESIGN: A human randomized, double-blinded, placebo-controlled crossover study combined with a confirmatory in-situ study of perfused rat intestines.SETTING: Aarhus University Hospital.Methods: Fifteen healthy male participants were examined 2 x 2 times: An oral glucose tolerance test (OGTT) was performed on day one and an isoglycemic intravenous glucose infusion replicating the blood glucose profile of the OGTT day was performed on day two. These pairs of study days were repeated on treatment with melatonin and placebo, respectively. For the in-situ study, six rat intestines and four rat pancreases were perfused arterially with perfusion buffer ± melatonin. The intestines were concomitantly perfused with glucose through the luminal compartment.RESULTS: In humans, melatonin treatment resulted in reduced GIP secretion compared with placebo (ANOVA p=0.003), an effect also observed in the perfused rat intestines (ANOVA p=0.003) in which GLP-1 secretion also was impaired by arterial melatonin infusion (ANOVA p<0.001). Despite a decrease in GIP levels, the in-vivo glucose-stimulated insulin secretion was unaffected by melatonin (p=0.78).CONCLUSION: Melatonin reduced GIP secretion during an oral glucose challenge in healthy young men but did not affect insulin secretion. Reduced GIP secretion was confirmed in an in-situ model of the rat intestine.

U2 - 10.1210/clinem/dgab521

DO - 10.1210/clinem/dgab521

M3 - Journal article

C2 - 34265066

VL - 106

SP - e5109-e5123

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -