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1 Center for Circadian Biology and Medicine, Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208; and 2 Center for the Study of Biological Rhythms, Free University of Brussels, Erasme Campus, B-1070 Brussels, Belgium
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
-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.
suprachiasmatic nucleus; circadian rhythm; diabetes; hyperglycemia; insulin; hypoglycemia
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