Theophylline disrupts diurnal rhythms of humoral factors with loss of meal cyclicity

To test the possibility that theophylline induced circadian disappearance of food intake might depend upon rhythmic disruption of blood glucose, insulin and free fatty acids (FFA), theophylline was administered chronically. This markedly lengthened postprandial intermeal intervals during the dark, and induced approximately identical intermeal intervals and identical meal sizes in the light and dark periods. In contrast to the clear light-dark dependent oscillations of serum glucose, insulin and FFA in the controls, the theophyllinized rats lost circadian fluctuation of each of these three chemical substances. Further, theophyllinized rats, unlike controls, had no time-dependent fluctuation in the levels of these substances at ? 120, ?60 or ?15 min preceding the onset of the first meal before the dark. These findings, together with previous reports, explain the disappearance of nocturnal feeding rhythm in theophyllinized rats in terms of functional destruction of circadian regulation in the hypothalamus which modulate the production of chemical determinants of food intake.