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.
Hsu
B R-S
BR
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang-Gung Memorial Hospital, Linkou Medical Center, Kueishan County, Taoyuan Hsien, Taiwan.
Chen
S-T
ST
Fu
S-H
SH
D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011524:Protoporphyrins / Q000494:pharmacology*
D005938:Glucocorticoids; D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin; D006419:Heme Oxygenase (Decyclizing)