Cobalt-Protoporphyrin treatment renders islets tolerant to interleukin-1 beta suppression.
This study examined whether treating donor mice with a single dose of cobalt protoporphyrin (CoPP) induced heme oxygenase-1 (HO-1) and protected islet cells from interleukin-1 beta (IL-1 beta) suppression. Islets were isolated from mice receiving a single dose of either CoPP (20 mg/kg of body weight, CoPP islets) or isotonic NaCl solution vehicle (control islets), 24 hours before isolation. Glucose-stimulated insulin secretion (GSIS) and insulin content (IC) of the islets were determined following incubation in the presence versus absence of murine IL-1 beta for 21 or 65 hours. The HO-1 protein level of CoPP-induced islets, as determined by an enzyme immunoassay, was significantly higher than that of control islets at 12 hours (P <.01) and 30 hours (P <.05), and returned to basal levels at 56 hours (P = NS). Following a 21-hour incubation with IL-1 beta, CoPP islets secreted significantly more insulin upon glucose stimulation and preserved significantly more IC than control islets. After 65-hour incubation with IL-1 beta, CoPP islets secreted significantly less insulin upon glucose stimulation than control islets and preserved significantly less IC compared to islets incubated without IL-1 beta. In conclusion, treatment with cobalt-protoporphyrin to induce heme oxygenase-1 protects islets against the suppressive effects of IL-1 beta.
Hsu
B R-S
BR
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang-Gung Memorial Hospital, Linkou Medical Center, Taiwan. bh0658@adm.cgmh.org.tw
Juang
J-H
JH
Chen
S-T
ST
Hsu
S
S
Fu
S-H
SH
D000818:Animals; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011524:Protoporphyrins / Q000494:pharmacology*; D013997:Time Factors
D007328:Insulin; D007375:Interleukin-1; D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin