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Cortisol
12
Growth
Adiposite hormone
Melatonin
Lipid
absorption
Heart
Fig. 1. The diurnal rhythm of hormones
and some metabolic processes. The release attacks
of leptin hormone occurs in a circadian cy-
cle, and serum leptin levels peak at night. 9 3
The levels of growth hormone peak be-
tween 02: 00 and 04: 00 a.m. The cortisol
concentration in circulation reaches a peak
level just before waking in the morning.
İnsulin secretion decrease at night (espe-
cially between 03:00 and 05:00 a.m.). Syn-
Insulin
thesis and release of melatonin is stimulat-
ed in the dark at night, while it is sup-
pressed by light during the day. Lipid
6
absorption in the dark phase is higher than
in the light phase. Myocardial infarction
peak at night or early in the morning.
Table 1. Genes of the circadian rhythm and their roles [2] In mammals, circadian clock homeostasis is enabled
by feedback (negative) and feed-forward (positive)
Gene Role in circadian rhythm mechanisms influencing transcription, translation, and
Per 1 PER/CRY interaction, CLOCK/BMAL1 inhibitor post-translational events [5, 29]. The transcriptional
Per 2 PER/CRY interaction, CLOCK/BMAL1 inhibitor feedback pattern is mediated through the Cry1, Cry2,
Per 3 PER/CRY interaction Per1, and Per2 proteins. The CLOCK and BMAL1 pro-
Cry 1 Interaction with PERs, CLOCK/BMAL1 inhibitor teins bind to the E-promoter region on the Per and Cry
Cry 2 Interaction with PERs, CLOCK/BMAL1 inhibitor genes and induce their expression. At a later stage, Per
Tim Dimerization with PER
CLOCK Transcription factor and Cry heterodimerize and translocate from the cyto-
BMAL1 Transcription factor plasm to the nucleus to inhibit CLOCK/BMAL1-induced
gene expression [37, 39]. This negative feedback mecha-
nism is important for the circadian system to work effec-
tively.
ulation of glucose metabolism. Insulin sensitivity and
glucose uptake are impaired in rats with lesions in their
SCN [36]. Deterioration in the circadian clock can lead to Circadian Rhythm and Energy Homeostasis
impaired insulin secretion and hypoinsulinemia [29].
Circadian rhythm-related CLOCK and BMAL1 proteins Energy metabolism is regulated by many hormones,
are involved in the production and release of insulin by enzymes, and transport systems, and circadian rhythm
binding to the circadian rhythm-regulating distal regions effectively modulates their expression, secretion, and/or
of pancreatic β-cells [37]. Both Type 1 and 2 diabetes have activation [40]. The metabolic pathways that provide en-
insulin insufficiency or absence due to β-cell damage. ergy homeostasis are coordinated by metabolites that
Therefore, the role of circadian rhythm in the etiology of propose changes and proactively prepare the molecular
diabetes should not be overlooked in terms of β-cell dam- environment as well as acute signaling systems that re-
age [38]. Clock genes and tasks regulating circadian spond instantaneously to changes in circadian clocks
rhythms in mammals are summarized in Table 1 [2]. [41].