F. Saraviafernandez et al., ENVIRONMENTAL AND EXPERIMENTAL PROCEDURES LEADING TO VARIATIONS IN THE INCIDENCE OF DIABETES IN THE NONOBESE DIABETIC (NOD) MOUSE, Autoimmunity, 24(2), 1996, pp. 113-121
Environmental factors appear to be nongenetic risks of importance in t
he progression of insulin-dependent diabetes mellitus (IDDM) or type 1
diabetes, whose mechanisms are not yet well understood. Stressful lif
e events, in particular, have been linked to the expression of overt d
iabetes in humans. However, in rodent models of IDDM, contradictory da
ta exist concerning the effects of stress on the disease. Here, we sho
w that a stressor, such as long-term repeated injections of vehicle (0
.9% saline), was able to delay the appearance and/or decrease the inci
dence of diabetes in both sexes of NOD mice. Short-term chronic stress
applied from the 6th to the 8th week of age by a combination of multi
ple stressors (overcrowding + immobilization + cold exposure + anesthe
sia) protected NOD mice from diabetes, particularly males. In contrast
, prenatal stress, induced by immobilization of the mothers during the
third part of pregnancy, accelerated the onset and increased the prev
alence of diabetes at 30 weeks of age in NOD females, while it had no
effect in males. Finally, adrenalectomy appears to aggravate the devel
opment of diabetes in NOD mice, particularly in males. In conclusion,
these data demonstrate that the appearance of diabetes in NOD mice is
extremely sensitive to various experimental and environmental conditio
ns. These results are discussed in the context of the complex neuroend
ocrine-immune interactions which occur during the progression of IDDM,
with a particular focus on glucocorticoids and cytokines.