Secretion of glucagon, GLP-1 and GIP may be affected by circadian rhythm in healthy males

Abstract

Abstract Background Glucagon is secreted from pancreatic alpha cells in response to low blood glucose and increases hepatic glucose production. Furthermore, it enhances hepatic protein and lipid metabolism during a mixed meal. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from gut endocrine cells during meals and control glucose homeostasis by potentiating insulin secretion and inhibits food intake. Both glucose control and food intake have been reported to be affected by circadian rhythms and vice versa. In this study, we investigated whether the secretion of glucagon, GLP-1 and GIP was affected by circadian rhythms. Methods A total of 24 healthy men with regular sleep schedules were examined for 24 hours at the hospital ward with 15 hours of wakefulness and 9 hours of sleep. Food intake was standardized, and blood samples were obtained every third hour. Plasma concentrations of glucagon, GLP-1 and GIP were measured, and data were analyzed by rhythmometric statistical methods. Available data on plasma glucose and plasma C-peptide were also included. Results Plasma concentrations of glucagon, GLP-1, GIP, C-peptide and glucose fluctuated with a diurnal 24-hour rhythm, with the highest levels during the day and the lowest levels during the night: glucagon (p<0.0001, peak time 18:26h), GLP-1 (p<0.0001, peak time 17:28h), GIP (p<0.0001, peak time 18:01h), C-peptide (p<0.0001, peak time 17.59h), and glucose (p<0.0001, peak time 23:26h). As expected, we found significant correlations between the levels of C-peptide and GLP-1 and GIP, but not between glucagon, GLP-1 and GIP and glucose. Conclusions Our results demonstrate that plasma levels of glucagon, GLP-1 and GIP follow a diurnal, most likely circadian rhythm in young healthy males that appear independent of food intake. These findings underpin disturbed circadian rhythm as a potential risk factor for diabetes and obesity. Trial registration ClinicalTrials.gov Identifier: NCT06166368. Registered 12 December 2023.