Serum transforming growth factor beta 1 during diabetes development in non-obese diabetic mice and humans

Olivieri A;De Angelis S;Dionisi S;D'Annunzio G;Locatelli M;Marinaro M;Bonato V;Amendola A;Songini M;VELLUZZI, FERNANDA;Schirru C;Cotichini R;Stazi MA;Dotta F;Lorini R;Bottazzo GF;Boirivant M.

2010-01-01

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Abstract

Recent data show that regulatory cells with transforming growth factor (TGF)-b1-dependent activity are able to restore self-tolerance in overtly diabetic non-obese diabetic (NOD) mice. Thus, TGF-b1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF-b1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one isletrelated antibody. Serum TGF-b1 (both total and active) was measured by enzyme-linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow-up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice.TGF-b1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF-b1 (aTGF-b1) serum levels. In mice, aTGF-b1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin-positive cells. Our findings suggest that in NOD mice serum TGF-b1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF-b1 in islet-related antibody-positive subjects may provide insights into the natural history of prediabetic phase of T1D.