Fig. 3.

Effect of misalignment between the central clock and the behavioural/environmental cycle on glucose tolerance. (a) In-laboratory experimental conditions designed to test the effect of alignment vs misalignment on glucose tolerance. In the alignment condition, room light and wake occur during the circadian day, when melatonin is low. A test meal (blue arrow) is given during the wake period to assess glucose tolerance during alignment. In the misalignment condition, room light and wake occur during the circadian night, when circadian drive for melatonin production is high. A test meal (orange arrow) is given during the wake period to assess glucose tolerance during misalignment. (b, c) Glucose tolerance is impaired in misaligned vs aligned conditions during in-laboratory experimental protocols of both gradual and rapid misalignment. In a forced desynchrony protocol (b), in which misalignment is gradual (see text for more details), postprandial glucose and late-phase postprandial insulin (timing of meal indicated by black bar) were higher in the misaligned (orange closed circles) vs aligned (blue open circles) condition (n = 10; mean ± SEM; p<0.001 and p<0.06, respectively, with statistical significance for effect of misalignment). In a simulated shift-work protocol (c), in which misalignment occurred rapidly (see text for more details), postprandial glucose and insulin were both higher in the misaligned (orange closed circles) vs aligned (blue open circles) condition (n = 14; mean ± SEM; p=0.013 and p=0.001, respectively). In both experimental protocols, the results indicated that circadian misalignment impaired glucose tolerance, in part via reduced insulin sensitivity. Data in (b, c) adapted from [20] and [21] under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium. This figure is available as part of a downloadable slideset.