The suprachiasmatic nucleus (SCN), the biological clock, is responsible for
a 24-h rhythm in plasma glucose concentrations, with the highest concentra
tions toward the beginning of the activity period. To investigate whether t
he SCN is also responsible for daily fluctuations in glucose uptake and to
examine how these fluctuations relate to the rhythm in plasma glucose conce
ntrations, SCN-intact rats and SCN-lesioned rats were injected intravenousl
y with a glucose bolus at different time points. We found an increase in gl
ucose uptake toward the beginning of the activity period, followed by a gra
dual reduction in glucose uptake toward the end of the activity period. The
daily variation in glucose tolerance seemed not to be caused by fluctuatio
ns in insulin responses of the pancreas but by a daily variation in insulin
sensitivity. Lesioning the SCN resulted in the disappearance of the daily
fluctuation in glucose uptake and insulin sensitivity. Interestingly, SCN-l
esioned rats showed an enhancement in glucose tolerance that could not be e
xplained by higher insulin responses or enhanced insulin sensitivity. There
fore, these findings suggest a role for the SCN in insulin-independent gluc
ose uptake. The present results further show that the daily rhythm in gluco
se tolerance follows the same pattern as the daily rhythm in plasma glucose
concentrations. We hypothesized that the biological clock prepares the ind
ividual for the upcoming activity period by two separate mechanisms: increa
sing plasma glucose concentrations and making tissue more tolerant to gluco
se.