The Effect of Melatonin on Incretin Hormones: Results From Experimental and Randomized Clinical Studies

• Published in: The journal of clinical endocrinology and metabolism 2021-12, Vol.106 (12), p.e5109-e5123
• Main Authors: Lauritzen, Esben Stistrup, Støy, Julie, Bæch-Laursen, Cecilie, Grarup, Niels, Jessen, Niels, Hansen, Torben, Møller, Niels, Hartmann, Bolette, Holst, Jens Juul, Kampmann, Ulla
• Format: Article
• Language: English
• Subjects: Adult; Animals; Antioxidants - pharmacology; Blood Glucose - analysis; Blood sugar; Clinical trials; Cross-Over Studies; Double-Blind Method; Follow-Up Studies; Gastric Inhibitory Polypeptide - metabolism; Glucagon; Glucagon-Like Peptide 1 - metabolism; Glucose Tolerance Test; Glucose tolerance tests; Healthy Volunteers; Humans; Incretins - metabolism; Insulin Secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Intestines - drug effects; Intestines - metabolism; Male; Melatonin; Melatonin - pharmacology; Rats; Rats, Wistar; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgab521

Glucose homeostasis is under circadian control through both endocrine and intracellular mechanisms, with several lines of evidence suggesting that melatonin affects glucose homeostasis. To evaluate the acute in vivo and in situ effects of melatonin on secretion of the incretin hormones, glucagon-like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), and their impact on β-cell insulin secretion. A human randomized, double-blinded, placebo-controlled crossover study combined with a confirmatory in situ study of perfused rat intestines. Aarhus University Hospital. Fifteen healthy male participants were examined 2 × 2 times: an oral glucose tolerance test (OGTT) was performed on day 1 and an isoglycemic IV glucose infusion replicating the blood glucose profile of the OGTT day was performed on day 2. These pairs of study days were repeated on treatment with melatonin and placebo, respectively. For the in situ study, 6 rat intestines and 4 rat pancreases were perfused arterially with perfusion buffer ± melatonin. The intestines were concomitantly perfused with glucose through the luminal compartment. 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