Influence of C-peptide on early glomerular changes in diabetic mice.

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. 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. 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. 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.

Maezawa Y ，Yokote K ，Sonezaki K ，Fujimoto M ，Kobayashi K ，Kawamura H ，Tokuyama T ，Takemoto M ，Ueda S ，Kuwaki T ，Mori S ，Wahren J ，Saito Y ... -  《DIABETES-METABOLISM RESEARCH AND REVIEWS》

Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production.

Krag S ，Nyengaard JR ，Wogensen L 《NEPHROLOGY DIALYSIS TRANSPLANTATION》

Angiotensin II stimulates alpha3(IV) collagen production in mouse podocytes via TGF-beta and VEGF signalling: implications for diabetic glomerulopathy.

Chen S ，Lee JS ，Iglesias-de la Cruz MC ，Wang A ，Izquierdo-Lahuerta A ，Gandhi NK ，Danesh FR ，Wolf G ，Ziyadeh FN ... -  《NEPHROLOGY DIALYSIS TRANSPLANTATION》

Galectin-9 inhibits glomerular hypertrophy in db/db diabetic mice via cell-cycle-dependent mechanisms.

Baba M ，Wada J ，Eguchi J ，Hashimoto I ，Okada T ，Yasuhara A ，Shikata K ，Kanwar YS ，Makino H ... -  《JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY》

Tranilast prevents the progression of experimental diabetic nephropathy through suppression of enhanced extracellular matrix gene expression.

Akahori H ，Ota T ，Torita M ，Ando H ，Kaneko S ，Takamura T ... -  《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》