Serum transforming growth factor β1 during diabetes development in non‐obese diabetic mice and humans

Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy.
Clinical & Experimental Immunology (Impact Factor: 3.04). 12/2010; 162(3):407-14. DOI: 10.1111/j.1365-2249.2010.04253.x
Source: PubMed


Recent data show that regulatory cells with transforming growth factor (TGF)-β1-dependent activity are able to restore self-tolerance in overtly diabetic non-obese diabetic (NOD) mice. Thus, TGF-β1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF-β1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet-related antibody. Serum TGF-β1 (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-β1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF-β1 (aTGF-β1) serum levels. In mice, aTGF-β1 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-β1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF-β1 in islet-related antibody-positive subjects may provide insights into the natural history of prediabetic phase of T1D.

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Available from: Francesco Dotta
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    • "T1D and its control group were matched for several factors (Table 1) including age and the sole documented criteria for exception were FBS as a marker of diabetes. Due to the fact that we had tried to control measurable factors, it appeared logical to suspect that the significant difference observed in the level of serum TGF-β could be related to diabetes and this finding was in accordance with previous observations [22–26]. "
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