Relationship of stressful housing conditions to the onset of diabetes mellitus induced by multiple, sub-diabetogenic doses of streptozotocin in mice.

The effect of the stress of crowded housing conditions (10 mice/cage) on the onset of diabetes after multiple, sub-diabetogenic doses of streptozotocin (MSZ) in male C57BL/KsJ mice was investigated. Prior to MSZ treatment, the group-housed and individually-housed animals had similar plasma glucose levels, while the former group's plasma corticosterone (CS) levels were elevated (54 +/- 8 ng/ml, p less than 0.03; 166% of the latter group). The group-housed animals became hyperglycemic (253 +/- 23 mg/dl) 2 days after the MSZ (day 7), with maximum hyperglycemia (506 +/- 23 mg/dl) developing by day 10. The individually housed animals did not become hyperglycemic until day 10 (303 +/- 24 mg/dl, p less than 0.001), and did not reach maximal hyperglycemia until between days 31 and 46, when plasma glucose levels were no longer different from the group-housed mice (507 +/- 37 mg/dl). There was a significant and progressive rise in CS levels of the stressed animals, reaching 218 +/- 25 ng/ml at day 46. The rise in CS of the unstressed animals was not significant until day 46, when the mean value reached 96 +/- 19 ng/ml (p less than 0.001 vs. basal). However, even at the conclusion of the experiment, the mean CS in the stressed animals was still 227% of that in the unstressed group (p less than 0.001). These studies demonstrate that the effects of stress (biochemically documented as an increase in CS levels) act synergistically with streptozotocin to promote an earlier onset of diabetes mellitus in males of this murine strain.