Interleukin-1 effect on glycemia in the non-obese diabetic mouse at the pre-diabetic stage.
Cytokines, particularly interleukin 1 (IL-1) and tumor necrosis factor, are known to induce hypoglycemia in normal rodents or different experimental models of type II diabetes. We investigated, at the pre-diabetic stage, the effect of short-term administration of murine recombinant interleukin-1 alpha (mrIL-1 alpha) on the levels of glucose, insulin and corticosterone in the non-obese diabetic (NOD) mouse, a spontaneous model of type I diabetes. Two-month-old, pre-diabetic NOD mice of both sexes were insensitive to mrIL-1 alpha (12.5 and 50 micrograms/kg) 2 h after administration, the time at which the maximal decrease (around 50%) was observed in the C57BL/6 mouse strain. Kinetic studies however showed that mrIL-1 alpha lowered glycemia in both sexes of NOD mice, but the effect was limited and delayed. In the NOD and C57BL/6 strains, mrIL-1 alpha had no influence on insulin levels in females, but significantly increased them in males (P < 0.0001). Castration of NOD males abrogated the stimulatory effect of mrIL-1 alpha on insulin secretion. Corticosterone secretion was stimulated by mrIL-1 alpha in both sexes of NOD and C57BL/6 mice, and this effect was faster and greater in NOD females than in C57BL/6 females. The incomplete hypoglycemic response to mrIL-1 alpha in females may be attributed to the anti-insulin effect of glucocorticoids, an effect which can be demonstrated when mrIL-1 alpha is administered to adrenalectomized animals or when mrIL-1 alpha is administered together with the glucocorticoid antagonist RU38486. In NOD males, in contrast, glucocorticoids did not play a major role in the limited hypoglycemic response to mrIL-1 alpha, since RU38486 and adrenalectomy were not able to unmask a hypoglycemic effect. Moreover, NOD mice of both sexes were less sensitive than C57BL/6 mice to the hypoglycemic effect of insulin (2.5 U/kg), which suggests some degree of insulin-resistance in NOD mice. With regard to the effect of IL-1 on NOD mouse glycemia, therefore, these results suggest that glucocorticoids and/or androgens, according to the animal's sex, may induce a state of insulin-resistance.
Amrani
A
A
CNRS URA 1461, Université de Paris V, Hôpital Necker, France.
Jafarian-Tehrani
M
M
Mormède
P
P
Durant
S
S
Pleau
J M
JM
Haour
F
F
Dardenne
M
M
Homo-Delarche
F
F
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D015735:Mifepristone / Q000494:pharmacology; D009919:Orchiectomy; D011236:Prediabetic State / Q000378:metabolism*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D007375:Interleukin-1; D015735:Mifepristone; D003345:Corticosterone; D006854:Hydrocortisone