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Review
. 2022 Jun;45(6):471-482.
doi: 10.1016/j.tins.2022.03.010. Epub 2022 Apr 21.

Circadian clock, diurnal glucose metabolic rhythm, and dawn phenomenon

Fei Peng  1 , Xin Li  2 , Fang Xiao  3 , Ruxing Zhao  4 , Zheng Sun  5
Affiliations
Review

Circadian clock, diurnal glucose metabolic rhythm, and dawn phenomenon

Fei Peng et al. Trends Neurosci. 2022 Jun.

Abstract

The circadian clock provides cue-independent anticipatory signals for diurnal rhythms of baseline glucose levels and glucose tolerance. The central circadian clock is located in the hypothalamic suprachiasmatic nucleus (SCN), which comprises primarily GABAergic neurons. The SCN clock regulates physiological diurnal rhythms of endogenous glucose production (EGP) and hepatic insulin sensitivity through neurohumoral mechanisms. Disruption of the molecular circadian clock is associated with the extended dawn phenomenon (DP) in type 2 diabetes (T2D), referring to hyperglycemia in the early morning without nocturnal hypoglycemia. The DP affects nearly half of patients with diabetes, with poorly defined etiology and a lack of targeted therapy. Here we review neural and secreted factors in physiological diurnal rhythms of glucose metabolism and their pathological implications for the DP.

Keywords: GABA; SCN; circadian rhythm; diabetes; metabolism; neuron.

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Conflict of interest statement

Declaration of interests The authors declare no interests.

Figures

Figure 1.
Figure 1.. Pathways connecting the central clock activity and peripheral metabolic rhythms.
The schematic illustrates the key neurohumoral pathways connecting the SCN central clock with the peripheral metabolic organs in the regulation of diurnal rhythmicity in baseline endogenous glucose production (EGP), glucose tolerance, and insulin sensitivity. Abbreviations: SNS, sympathetic nervous system; PSNS, parasympathetic nervous system; GH, growth hormone; IGF, insulin-like growth factor.
Figure 2.
Figure 2.. Endogenous glucose production (EGP) and its sensitivity to insulin-mediated suppression in healthy individuals and in the extended dawn phenomenon.
In normal physiology, baseline EGP and its sensitivity to insulin-mediated suppression both peak at wakening. Disruption of the clock-mediated insulin sensitivity rhythmicity at waking can lead to reduced insulin sensitivity at this time point and contribute to the extended dawn phenomenon in type 2 diabetes (T2D). The schematic illustrates one pattern of disruption out of many possible different ways of disruption.
See this image and copyright information in PMC

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