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The effects of insulin and glucocorticoid on granuloma formation and angiogenesis were studied using an adjuvant pouch in mice and a carrageenin pouch in rats. Carrageenin-induced granuloma formation was suppressed in the diabetic state induced by alloxan in rats. The suppression was restored by adrenalectomy. Corticosterone counteracted the restoration, whereas epinephrine did not, suggesting that the effects of adrenalectomy are due to the lack of adrenocortical hormones rather than epinephrine. The blood corticosterone levels in alloxan mice increased, following the increase of glucose level, to more than 20 micrograms/dl after 4 weeks. The increase of corticosterone levels disappeared after adrenalectomy. In the mouse adjuvant pouch, corticosterone dose-dependently decreased granuloma formation and angiogenesis. The values of these two parameters obtained with a dose of 20 micrograms/pouch corticosterone agreed with those of the serum levels in diabetic mice. Insulin dose-dependently reversed the suppressed angiogenesis of 20 micrograms corticosterone-treated mice and the dose-response curve approximated the curve of alloxan-treated mice. The effects of diabetes were concluded to involve insulin deficiency as well as glucocorticoid enhancement and the counteraction between the two may control granuloma formation and angiogenesis.

Involvement of glucocorticoid in insulin-induced angiogenesis of adjuvant pouch granuloma in diabetic mice.