Longitudinal study of islet cell antibodies and insulin autoantibodies and development of diabetes in non-obese diabetic (NOD) mice

Abstract

SUMMARYWe have previously shown the presence of circulating islet cell cytoplasmic antibodies (ICA) and insulin autoantibodies (IAA) in the NOD mouse before onset of insulin-dependent diabetes mellitus (IDDM), Here we have determined the levels ofthe two autoantibodies in 28 female NOD miee longiludinaliy from approximately day 40 to day 250, to examine their ontogeny, association and predictive value for diabetes. All animals (11 diabetic, 17 non-diabetie) showed varying levels of ICA at some stage, while IAA aetivity was found in 21 out of 28 mice. Expression ofboth the markers was seen in more than half of the animals by day 60. with higher levels and rates oecurring subsequently in both diabetie and non-diabetic groups. The expression of ICA did not always correlate with that of IAA. There was no apparent diflferenee in the ontogeny of ICA and IAA between the two groups. During the study period the number of animals with ICA was similar in the two groups, while the number of those with IAA was higher in the diabetic animals. In this group deelining and rising levels of ICA were seen just before elinical diabetes with frequent peaks of IAA. In the same animals, eight out of 11 mice showed eo-expression of high levels of both markers either intermittently or f>ersistently prior to onset, whereas only one non-diabetic animal showed this. We conclude that the ontogeny and serum level of ICA or TAA alone could not be used to prediet Ihe clinical onset of diabetes in these animals. However, co-expression of high levels ofboth markers prior to onset may suggest a strong predisposition to clinical diabetes. This may have relevance to attempts to predict the onset of IDDM in humans who have one or both of these immunologieal markers.

Receptor for advanced glycation end-products (RAGE) provides a link between genetic susceptibility and environmental factors in type 1 diabetes

“…sRAGE, soluble RAGE in NODLt mice, in whom seroconversion appears concurrently with a decrease in circulating soluble RAGE concentrations [41]. There was also an inverse relationship between circulating CML (an AGE) and either soluble RAGE concentrations or islet RAGE expression seen in both NODLt and NODScid mice.…”