Proinsulin and heat shock protein 90 as biomarkers of beta-cell stress in the early period after onset of type 1 diabetes.
Transl Res
; 168: 96-106.e1, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26397425
ABSTRACT
Rapid evaluation of therapies designed to preserve ß cells in persons with type 1 diabetes (T1D) is hampered by limited availability of sensitive ß-cell health biomarkers. In particular, biomarkers elucidating the presence and degree of ß-cell stress are needed. We characterized ß-cell secretory activity and stress in 29 new-onset T1D subjects (10.6 ± 3.0 years, 55% male) at diagnosis and then 8.2 ± 1.2 weeks later at first clinic follow-up. We did comparisons with 16 matched healthy controls. We evaluated hemoglobin A1c (HbA1c), ß-cell function (random C-peptide [C] and proinsulin [PI]), ß-cell stress (PIC ratio), and the ß-cell stress marker heat shock protein (HSP)90 and examined these parameters' relationships with clinical and laboratory characteristics at diagnosis. Mean diagnosis HbA1c was 11.3% (100 mmol/mol) and 7.6% (60 mmol/mol) at follow-up. C-peptide was low at diagnosis (P < 0.001 vs controls) and increased at follow-up (P < 0.001) to comparable with controls. PI did not differ from controls at diagnosis but increased at follow-up (P = 0.003) signifying increased release of PI alongside improved insulin secretion. PIC ratios and HSP90 concentrations were elevated at both time points. Younger subjects had lower C-peptide and greater PI, PIC, and HSP90. We also examined islets isolated from prediabetic nonobese diabetic mice and found that HSP90 levels were increased â¼4-fold compared with those in islets isolated from matched CD1 controls, further substantiating HSP90 as a marker of ß-cell stress in T1D. Our data indicate that ß-cell stress can be assessed using PIC and HSP90. This stress persists after T1D diagnosis. Therapeutic approaches to reduce ß-cell stress in new-onset T1D should be considered.
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Base de dados:
MEDLINE
Assunto principal:
Proinsulina
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Estresse Fisiológico
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Proteínas de Choque Térmico HSP90
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Diabetes Mellitus Tipo 1
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Células Secretoras de Insulina
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article