Altered circadian responses to light in streptozotocin-induced diabetic mice

Abstract

Diabetes mellitus affects the daily expression of many behavioral and metabolic processes. Recent studies indicate that changes in brain glucose metabolism alter the entraining effects of light of the circadian pacemaker. To test whether diabetes-associated diurnal changes are related to alterations in the responses of the circadian pacemaker to light, photic phase resetting of the circadian rhythm of locomotor activity was analyzed in diabetic mice housed in constant darkness. Multiple low doses of streptozotocin, which damages pancreatic β-insulin-producing cells, were used to render C57BL/6J mice mildly diabetic. In those mice treated with streptozotocin, serum glucose was increased by 25% and circadian responses to light either were increased by 40% for phase delays or were close to those observed in control animals for phase advances. Furthermore, insulin-induced hypoglycemia normalized light-induced phase delays in diabetic animals, without altering those in nondiabetic mice. These results show that abnormalities of daily temporal organization associated with diabetes can result from altered circadian responses to the daily variation in ambient light. Such alterations could be normalized with appropriate insulin therapy.