Skeletal Muscle Insulin Sensitivity Show Circadian Rhythmicity Which Is Independent of Exercise Training Status

Abstract

Circadian rhythms can be perturbed by shift work, travel across time zones, many occupational tasks, or genetic mutations. Perturbed circadian rhythms are associated with the increasing problem of obesity, metabolic dysfunction, and insulin resistance. We hypothesized that insulin sensitivity in skeletal muscle follows a circadian pattern and that this pattern is important for overall metabolic function. This hypothesis was verified using mice as a model system. We observed circadian rhythmicity in whole body insulin tolerance, as well as in signaling pathways regulating insulin- and exercise-induced glucose uptake in skeletal muscle, including AKT, 5′-adenosine monophosphate-activated protein kinase (AMPK) and TBC1 domain family member 4 (TBC1D4) phosphorylation. Basal and insulin-stimulated glucose uptake in skeletal muscle and adipose tissues in vivo also differed between day- and nighttime. However, the rhythmicity of glucose uptake differed from the rhythm of whole-body insulin tolerance. These results indicate that neither skeletal muscle nor adipose tissue play a major role for the circadian rhythmicity in whole-body insulin tolerance. To study the circadian pattern of insulin sensitivity directly in skeletal muscle, we determined glucose uptake under basal and submaximal insulin-stimulated conditions ex vivo every sixth hour. Both insulin sensitivity and signaling of isolated skeletal muscle peaked during the dark period. We next examined the effect of exercise training on the circadian rhythmicity of insulin sensitivity. As expected, voluntary exercise training enhanced glucose uptake in skeletal muscle. Nevertheless, exercise training did not affect the circadian rhythmicity of skeletal muscle insulin sensitivity. Taken together, our results provide evidence that skeletal muscle insulin sensitivity exhibits circadian rhythmicity.

Housing temperature influences exercise training adaptations in mice

“…Most remarkably, the ET response on glucose metabolism was reduced by thermoneutral housing. ET at ambient temperature led to a robust increase in glucose tolerance and improved insulin-stimulated glucose uptake in skeletal muscle and WAT in agreement with many previous reports [45][46][47][48][49][50][51][52][53] . However, this effect was absent in thermoneutrally housed mice.…”

Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease

“…Understanding the origin of diurnal rhythms in glucose and insulin is challenging due to the diversity of physiological processes that simultaneously modulate such dynamics. These range from the temporal distribution of feeding ( 56 ), upstream control via the suprachiasmatic nucleus ( 61 ), circadian skeletal muscle insulin sensitivity and glucose uptake ( 62 ), and circadian clock genes ( 63, 64 ). Not surprisingly, uncovering the mechanisms underlying chronodisruption pose additional challenges, mostly because it is difficult to identify unequivocally what mechanisms break down, in what order, and how effects accumulate to lead to disease.…”

“…Accounting for the dynamic interactions between the stress and metabolic axes is key to fully understand multisystemic conditions and to make sense of experimental and clinical observations subject to diurnal variability ( 62, 66-69 ). To advance this, we have developed a first-generation mathematical model that considers the dynamic interactions between glucocorticoid hormones and the mechanisms underpinning glucose metabolism.…”

The Preventive Effects of Pterostilbene on the Exercise Intolerance and Circadian Misalignment of Mice Subjected to Sleep Restriction

“…that the more active in voluntary movement in light period in SR mice, the higher level of activity of AMPK and SIRT1. [ 50 ] Moreover, the rhythm of AMPK and SIRT1 both were restored with PTE treatment and was not notable different from the CON mice.…”

“…[ 37–39 ] Our results were consistent with the results of Nakahata et al., AMPK phosphorylation activity and SIRT1 deacetylation activity showed diurnal rhythm in CON mice. [ 40,49,50 ] SR did change the activity preferences in mice which interacted with the activity of AMPK and SIRT1. Our results were consistent with those of Basse et al.…”