title: Serum transforming growth factor β1 during diabetes development in non-obese diabetic mice and humans.
abstract: 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.
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Olivieri
authors.forename: S
authors.initials: S
authors.lastname: De Angelis
authors.forename: S
authors.initials: S
authors.lastname: Dionisi
authors.forename: G
authors.initials: G
authors.lastname: D'Annunzio
authors.forename: M
authors.initials: M
authors.lastname: Locatelli
authors.forename: M
authors.initials: M
authors.lastname: Marinaro
authors.forename: V
authors.initials: V
authors.lastname: Bonato
authors.forename: A
authors.initials: A
authors.lastname: Amendola
authors.forename: M
authors.initials: M
authors.lastname: Songini
authors.forename: F
authors.initials: F
authors.lastname: Velluzzi
authors.forename: C
authors.initials: C
authors.lastname: Schirru
authors.forename: R
authors.initials: R
authors.lastname: Cotichini
authors.forename: M A
authors.initials: MA
authors.lastname: Stazi
authors.forename: F
authors.initials: F
authors.lastname: Dotta
authors.forename: R
authors.initials: R
authors.lastname: Lorini
authors.forename: G F
authors.initials: GF
authors.lastname: Bottazzo
authors.forename: M
authors.initials: M
authors.lastname: Boirivant
mesh_terms: D000293:Adolescent; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D001323:Autoantibodies; D053773:Transforming Growth Factor beta1
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