title: Alpha-melanocyte stimulating hormone preserves islet graft survival through down-regulation of Toll-like receptors.
abstract: The induction of Toll-like receptors (TLRs) in β cells is involved in β-cell death and graft rejection after transplantation. This study investigated the ability of alpha-melanocyte stimulating hormone (α-MSH) to protect pancreatic islets and improve graft survival through regulation of TLRs. To test the effect of α-MSH on TLR regulation, we first isolated pancreatic islets from rats pretreated with/without α-MSH and assayed inflammatory cytokines and insulin release, and measured the expression of TLRs. Pancreatic islets were transplanted into the kidney capsule of a diabetes mellitus (DM) mouse with and without prior injection of α-MSH. The blood glucose levels were measured and TLR4 expression in transplanted kidney tissue was assessed. Islet morphology, including size and total mass, was improved in the α-MSH group compared to the control group. The expression of TLRs as well as nitric oxide and monocyte chemoattractant protein 1 production were decreased in islets isolated from α-MSH-treated rats. In DM mice, the normoglycemic ratio was higher in the α-MSH-treated group than in the sham group. Moreover, the high levels of TLR4 expression observed in DM kidney tissue were significantly decreased in islet-transplanted tissue with α-MSH. This study showed that α-MSH protects pancreatic islets from cell death and dysfunction through downregulation of TLRs. In conclusion, α-MSH could contribute to improved islet graft survival and function in pancreatic islet transplantation.
authors.affiliation: Asan Institute for Life Science, Asan Medical Centre, seoul, Republic of Korea.
authors.forename: E-J
authors.initials: EJ
authors.lastname: Jung
authors.forename: S-C
authors.initials: SC
authors.lastname: Kim
authors.forename: S-H
authors.initials: SH
authors.lastname: Jeong
authors.forename: J-Y
authors.initials: JY
authors.lastname: Lee
authors.forename: D-J
authors.initials: DJ
authors.lastname: Han
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D015536:Down-Regulation; D006085:Graft Survival / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D051193:Toll-Like Receptors / Q000187:drug effects* / Q000378:metabolism; D000521:alpha-MSH / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D051193:Toll-Like Receptors; D009569:Nitric Oxide; D000521:alpha-MSH