Short-term sleep deprivation with nocturnal light exposure alters time-dependent glucagon-like peptide-1 and insulin secretion in male volunteers

Abstract

The intestinal L cell is the principal source of glucagon-like peptide-1 (GLP-1), a major determinant of insulin release. Because GLP-1 secretion is regulated in a circadian manner in rodents, we investigated whether the activity of the human L cell is also time sensitive. Rhythmic fluctuations in the mRNA levels of canonical clock genes were found in the human NCI-H716 L cell model, which also showed a time-dependent pattern in their response to well-established secretagogues. A diurnal variation in GLP-1 responses to identical meals (850 kcal), served 12 h apart in the normal dark (2300) and light (1100) periods, was also observed in male volunteers maintained under standard sleep and light conditions. These findings suggest the existence of a daily pattern of activity in the human L cell. Moreover, we separately tested the short-term effects of sleep deprivation and nocturnal light exposure on basal and postprandial GLP-1, insulin, and glucose levels in the same volunteers. Sleep deprivation with nocturnal light exposure disrupted the melatonin and cortisol profiles and increased insulin resistance. Moreover, it also induced profound derangements in GLP-1 and insulin responses such that postprandial GLP-1 and insulin levels were markedly elevated and the normal variation in GLP-1 responses was abrogated. These alterations were not observed in sleep-deprived participants maintained under dark conditions, indicating a direct effect of light on the mechanisms that regulate glucose homeostasis. Accordingly, the metabolic abnormalities known to occur in shift workers may be related to the effects of irregular light-dark cycles on these glucoregulatory pathways.

A single night light exposure acutely alters hormonal and metabolic responses in healthy participants

“…The difference observed in glucose tolerance and insulin sensitivity could be due to the presence of melatonin in the DL session, as melatonin has been reported to inhibit insulin secretion in both rat insulinoma cells and pancreatic islets, thus influencing blood glucose (43, 44). Furthermore, light exposure during sleep deprivation in humans has been reported to increase insulin resistance compared to sleep deprivation in the darkness (45). The explanation being possible due to dysregulation of the SCN that coordinates peripheral organs and energy homeostasis, in addition to altered melatonin levels, which have been associated with increased insulin resistance in experimental animals (46), while melatonin secretion was inversely correlated with insulin in healthy humans (47).…”

Circadian System and Glucose Metabolism: Implications for Physiology and Disease

“…It should be pointed out that circadian misalignment protocols involve a collection of behavioral cycles [29, 31, 45] (e.g., sleep/wake, fasting/feeding, rest/activity, and posture cycles), as well as a light/dark cycle [46-51] that can be misaligned separately or in concert relative to the central circadian clock. Most protocols induce circadian misalignment by uncoupling overall behavioral cycles (the collection of all behavioral cycles) and/or light/dark cycles from the central circadian clock.…”

Matching Meals to Body Clocks—Impact on Weight and Glucose Metabolism

“…Whether there are circadian rhythms in the release of gut hormones is still poorly described, although GLP-1 has received considerable interest. In a series of in vitro and in vivo experiments, a clear circadian pattern in the release of GLP-1 from rat and human intestinal L cells has been reported [38,39,40]. This pattern is altered by circadian disruptors, including constant light exposure, a Western diet and altered meal patterning (i.e., feeding during the day in rats).…”

“…However, these initial studies did not account for inter-meal intervals, or the caloric loads of the meals administered [41,42,43]. Subsequent studies that controlled these conditions, and fed participants identical mixed-nutrient test meals, 12 h apart, also showed rhythmic patterns in basal and post-prandial GLP-1 and insulin concentrations [40]. In contrast with rodents, GLP-1 and insulin responses did not change in parallel, with highest GLP-1 secretion observed at 2300 h whereas the highest insulin response was noted at 1100 h [40].…”

“…Subsequent studies that controlled these conditions, and fed participants identical mixed-nutrient test meals, 12 h apart, also showed rhythmic patterns in basal and post-prandial GLP-1 and insulin concentrations [40]. In contrast with rodents, GLP-1 and insulin responses did not change in parallel, with highest GLP-1 secretion observed at 2300 h whereas the highest insulin response was noted at 1100 h [40]. This study showed that exposure to 22 h of constant light dampened the patterns of GLP-1 and insulin release, in association with insulin resistance.…”