Modelling of type 1 diabetes with monoclonal antibody ICA-1.
In order to investigate the possible role of pancreatic beta-cell p(64-69) antigens in the development of diabetes type 1, a monoclonal antibody (ICA-1) to the 64-69 kDa antigen family was produced and characterized. Short-term (0.25 mg per rat, intraperitoneally, daily for 9 days) and prolonged (0.125 mg per rat, intraperitoneally, three times a week for 8 weeks) administration of ICA-1 to Wistar rats caused the development of a diabetes-like reaction characterized by moderate hyperglycaemia, markedly reduced pancreatic insulin content, and depressed insulin secretion. After 9 days, histological changes in the pancreas indicative of early insulitis were also observed. Continued ICA-1 treatment increased mononuclear infiltration of the islets and progressive beta-cell damage became evident. In order to confirm the insulin-dependent character of this early-stage diabetes induced by ICA-1, rats were injected with insulin in liposomes, whereupon normalization of serum insulin levels was observed together with a decrease in mononuclear infiltration. These results indicate that the 64-69 kDa antigen family is closely related to the hypothetical primary target protein that may play a role in the development of autoimmune beta-cell destruction.
Petrov
R
R
Institute of Immunology, Ministry of Health of the USSR, Moscow.
Zlobina
E
E
Demin
Y u
Yu
Rossels
A
A
Bachurin
P
P
Dubinkin
I
I
Ryabkova
V
V
Brikova
S
S
Gudima
G
G
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000276:immunology*; D008081:Liposomes; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007328:Insulin; D008081:Liposomes; D005947:Glucose