Entrainment of ultradian oscillations in the secretion of insulin and glucagon to the nonrapid eye movement/rapid eye movement sleep rhythm in humans

Abstract

The cause of ultradian oscillations in the secretion of glucagon and insulin with a period length between 70-140 min has been atttributed to feedback mechanisms of glucose and insulin. Influences of the central nervous system on these ultradian glucagon and insulin oscillations remained to be elucidated. In the present study on one occasion, concentrations of glucose, glucagon, insulin, and GH were determined at 15-min intervals from 2100-0700 h in 16 healthy subjects while they were infused with saline solution. On another occasion, concentrations of these hormones during nocturnal sleep were determined in 10 of these subjects while they were constantly infused with glucose (4.5 mg/kg x min). The order of the treatments (placebo vs. glucose) was balanced across subjects, and experiments were performed in a double blind manner. Significant glucagon and insulin peaks were determined by the peak detection algorithm Cluster. Sleep was recorded somnopolygraphically. During the infusion of saline solution, glucagon concentrations showed spontaneous oscillations, with a mean periodicity of 107.9 +/- 13.2 min. During the constant infusion of glucose, oscillations of similar periodicity (110.1 +/- 10.3 min) were observed for insulin. The phases of glucagon and insulin secretory activity on the respective nights were entrained to the nonrapid eye movement (non-REM)/REM sleep cycle. Significant increases in the concentrations of glucagon (chi 5.23; P < 0.02) and insulin (chi= 7.32; P < 0.01) generally fell into epochs of non-REM sleep, with a preference for the beginning of the epochs, whereas decreasing concentrations of these hormones coincided significantly with epochs of REM sleep (P < 0.05). The time spent in the different sleep stages was not altered during glucose infusion. In conclusion, ultradian oscillations of insulin and glucagon concentrations are modulated by central nervous system mechanisms entraining secretory pulses of the alpha- and beta-cells of the endocrine pancreas to the non-REM sleep epochs of the non-REM/REM sleep cycle.