Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Transtornos Cognitivos/etiologia , Complicações do Diabetes/complicações , Síndrome Metabólica/complicações , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Humanos , Hiperglicemia/complicações , Hipertensão/complicações , Pessoa de Meia-IdadeAssuntos
Calcinose/tratamento farmacológico , Tecido Conjuntivo , Ácido Etidrônico/uso terapêutico , Dedos , Dor/tratamento farmacológico , Síndrome de Werner/tratamento farmacológico , Adenosina Trifosfatases/genética , Calcinose/diagnóstico por imagem , Tecido Conjuntivo/diagnóstico por imagem , DNA Helicases/genética , Análise Mutacional de DNA , Feminino , Dedos/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Radiografia , RecQ Helicases , Resultado do Tratamento , Síndrome de Werner/genéticaRESUMO
BACKGROUND: C-peptide has been shown to ameliorate diabetes-induced functional and structural renal changes in animal models as well as in patients with type 1 diabetes. This study aims to examine the molecular effects of C-peptide on early glomerular changes in a mouse model of type 1 diabetes. METHODS: Fourteen days after induction of diabetes by streptozotocin (STZ), the animals received rat C-peptide for either 24 h or 7 days. Urinary albumin excretion was measured by ELISA. Glomerular mRNA expression of the transforming growth factor (TGF)-beta(1) and type IV collagen was quantified by real-time PCR. The effect of C-peptide on type IV collagen gene expression in cultured murine podocytes was also examined. RESULTS: C-peptide decreased urinary albumin excretion from 0.29 to 0.18 microg/min (-40.7%, P < 0.01). The transcript level of (alpha3)IV collagen in glomeruli was up-regulated 2.2-fold in diabetic mice and was inhibited by 45-70% (P < 0.05) upon C-peptide treatment. C-peptide suppressed glomerular expression of TGF-beta(1) by 36.6% after 7 days (P < 0.05) but not 24 h after injection. In vitro studies using cultured podocytes revealed that C-peptide dose-dependently inhibited TGF-beta-induced up-regulation of type IV collagen. Moreover, both pertussis toxin (PTX) and a specific inhibitor for extracellular signal-regulated kinase (ERK) pathway reversed the inhibitory effect of C-peptide on TGF-beta. Finally, C-peptide was shown to up-regulate the activity of ERK in podocytes. CONCLUSIONS: These findings indicate that C-peptide suppresses specific aspects of early glomerular changes in a mouse model of diabetes and that the effect is at least in part mediated via interaction with the TGF-beta signal in glomerular podocytes.