A single-dose of cobalt-protoporphyrin protects islet beta cells from glucocorticoid suppression

This study examined whether treating donor mice with a single-dose of cobalt protoporphyrin (CoPP) could induce heme oxygenase-1 (HO-1) and thus protect islet cells from suppression by high-dose glucocorticoid. Islets were isolated from mice receiving either a single dose of CoPP (20 mg/kg body weight) (CoPP-islets) or isotonic sodium chloride solution (control islets) at 24 hours before isolation. Following incubation in the absence or presence of methylprednisolone (100 and 1000 ng/mL) for 24 hours, glucose-stimulated insulin secretion and insulin content of cultured islets were determined. Data were expressed as the mean +/- standard error. HO-1 protein level of CoPP-islets was significantly higher than that of normal islets at 12 hours (P < .005) and 30 hours (P < .05) but not at 56 hours after CoPP administration (P = NS). The expression of CPP-32, an apoptosis inducer, was significantly inhibited in CoPP-islets at 24 hours after CoPP administration. Compared to the control islets, CoPP-islets secreted significantly more insulin in response to glucose stimulation following 24-hour incubation with 100 and 1000 ng/mL of methylprednisolone (P < .05 and P < .05). The insulin content of both control and CoPP-islets did not differ significantly after 24-hour incubation with methylprednisolone. In conclusion, a single-dose treatment with cobalt-protoporphyrin for the induction of heme oxygenase-1 protects islets against the suppressive effect of methylprednisolone.