Circadian variation in alloxan sensitivity of mice as indicated by mortality and blood glucose alteration.
The objective of this study was to determine in mice if a time-dependent pancreatic beta-cell susceptibility to alloxan could be correlated to daily changes in blood glucose levels and to monitor the pattern of blood glucose at various times of day as mice became diabetic. Food was removed from mice standardized to a 12-h light:dark cycle (lights on at 0600 h CST, during the month of June) at 12 h before subcutaneous injection with 0.27 mg/g of alloxan. Six groups of 30 fasted mice were injected at 4-h intervals. Blood glucose levels were measured from each group immediately prior to injection, and at 2, 4, 8, 12, 24, 48, and 216 h after treatment. Animals receiving alloxan during the early- to middark period had an increase in blood glucose after 2 h, followed by a decline to hypoglycemic levels between 4 and 8 h, and recovery to hyperglycemic levels 48 h after alloxan exposure. Three and 30% of these animals were dead at 8 and 48 h, respectively. Mice treated during the midlight span had decreased blood glucose levels 2 h after alloxan treatment followed by an increase to diabetic hyperglycemia within 48 h. Twenty-three and 70% of the animals treated at 1430 h were dead at 8 and 48 h, respectively. At 216 h, total mortality was 45.6% and 81 of the 98 surviving mice were hyperglycemic. These data suggest a greater sensitivity to alloxan during the midlight resting period of the mice. This may be the result of increased sensitivity to the insulin released from the beta cells when alloxan was given during the light span.
Feuers
R J
RJ
Department of Health and Human Services, Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Mittelstaedt
R A
RA
Hunter
J D
JD
Saldivar
J
J
Tsai
T H
TH
Scheving
L E
LE
D000496:Alloxan / Q000008:administration & dosage / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002940:Circadian Rhythm; D003643:Death; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D001786:Blood Glucose; D000496:Alloxan