title: Effects of surface camouflaged islet transplantation on pathophysiological progression in a db/db type 2 diabetic mouse model.
abstract: To investigate the inhibition effects of pancreatic islet transplantation on the progression of obese type 2 diabetes, we analyzed the effects of surface camouflaged islet transplantation on delaying the disease progression in a db/db diabetic mouse model. Surface camouflaged islets using 6-arm-PEG-catechol were transplanted in db/db diabetic mice. The fat accumulation and toxicity in the liver, the expansion of islets in the pancreas, and the size change of abdominal adipocyte were analyzed. In addition, the blood glucose control, insulin levels and immunohistochemical staining of recovered tissues were analyzed after transplantation. Then co-administration of anti-CD154 monoclonal antibody and Tacrolimus (IT group) deterred the pathophysiological progression of obese type 2 diabetes. At day 3 of transplantation, the serum insulin concentration of IT group was increased compared to the db/db diabetic mice group. The immunohistochemical studies demonstrated that the mass of 6-arm-PEG-catechol grafted islet was preserved in the transplantation site for 14 days. Surface modification using 6-arm-PEG-catechol effectively inhibited the immune cell infiltration and activation of host immune cells when immunosuppressive drug was given to the db/db type 2 diabetes mice. Therefore, 6-arm-PEG-catechol grafted islets effectively restored the insulin secretion in islet recipients and prevented the disease progression in type 2 diabetes.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jee-Heon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Simmyung
authors.initials: S
authors.lastname: Yook
authors.forename: Haeshin
authors.initials: H
authors.lastname: Lee
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Ahn
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Lee
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D001786:Blood Glucose; D023201:CD40 Ligand / Q000008:administration & dosage / Q000276:immunology; D002396:Catechols / Q000138:chemical synthesis / Q000378:metabolism; D048430:Cell Shape; D048429:Cell Size; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D018450:Disease Progression; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage / Q000276:immunology; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D002396:Catechols; D007328:Insulin; D023201:CD40 Ligand; D011092:Polyethylene Glycols; C034221:catechol; D016559:Tacrolimus