Glucagon is secreted from pancreatic alpha cells in response to low blood glucose and increases hepatic glucose production. Furthermore, glucagon 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 inhibiting food intake. Both glucose homeostasis 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. A total of 24 healthy men with regular sleep schedules were examined for 24 h at the hospital ward with 15 h of wakefulness and 9 h 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. Plasma concentrations of glucagon, GLP-1, GIP, C-peptide and glucose fluctuated with a diurnal 24-h rhythm, with the highest levels during the day and the lowest levels during the night: glucagon (p < 0.0001, peak time 18:26 h), GLP-1 (p < 0.0001, peak time 17:28 h), GIP (p < 0.0001, peak time 18:01 h), C-peptide (p < 0.0001, peak time 17.59 h), and glucose (p < 0.0001, peak time 23:26 h). As expected, we found significant correlations between plasma concentrations of C-peptide and GLP-1 and GIP but did not find correlations between glucose concentrations and concentrations of glucagon, GLP-1 and GIP. Our results demonstrate that under meal conditions that are similar to that of many free-living individuals, plasma concentrations of glucagon, GLP-1 and GIP were observed to be higher during daytime and evening than overnight. These findings underpin disturbed circadian rhythm as a potential risk factor for diabetes and obesity. ClinicalTrials.gov Identifier: NCT06166368. Registered 12 December 2023.

中文翻译：

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健康男性胰高血糖素、GLP-1 和 GIP 的分泌可能受到昼夜节律的影响

胰高血糖素由胰腺α细胞分泌，以应对低血糖并增加肝葡萄糖的产生。此外，胰高血糖素可增强混合餐期间的肝脏蛋白质和脂质代谢。胰高血糖素样肽-1 (GLP-1) 和葡萄糖依赖性促胰岛素多肽 (GIP) 在进餐时从肠道内分泌细胞分泌，通过增强胰岛素分泌和抑制食物摄入来控制葡萄糖稳态。据报道，葡萄糖稳态和食物摄入都受到昼夜节律的影响，反之亦然。在本研究中，我们研究了胰高血糖素、GLP-1 和 GIP 的分泌是否受到昼夜节律的影响。共有 24 名有规律睡眠的健康男性在医院病房接受了为期 24 小时的检查，其中清醒时间为 15 小时，睡眠时间为 9 小时。食物摄入量被标准化，并且每三个小时采集一次血样。测量胰高血糖素、GLP-1和GIP的血浆浓度，并通过节律统计方法分析数据。还包括血浆葡萄糖和血浆 C 肽的可用数据。胰高血糖素、GLP-1、GIP、C 肽和葡萄糖的血浆浓度以昼夜 24 小时节律波动，白天水平最高，夜间水平最低：胰高血糖素（p < 0.0001，峰值时间 18： 26 小时）、GLP-1（p < 0.0001，峰值时间 17:28 小时）、GIP（p < 0.0001，峰值时间 18:01 小时）、C 肽（p < 0.0001，峰值时间 17.59 小时）和葡萄糖（p < 0.0001，峰值时间 23:26 小时）。正如预期的那样，我们发现 C 肽与 GLP-1 和 GIP 的血浆浓度之间存在显着相关性，但没有发现葡萄糖浓度与胰高血糖素、GLP-1 和 GIP 浓度之间的相关性。我们的结果表明，在与许多自由生活个体相似的膳食条件下，观察到胰高血糖素、GLP-1 和 GIP 的血浆浓度在白天和晚上比夜间更高。这些发现证实昼夜节律紊乱是糖尿病和肥胖症的潜在危险因素。ClinicalTrials.gov 标识符：NCT06166368。注册日期：2023 年 12 月 12 日。