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Updated: Aug 13, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Influence of C-peptide on early glomerular changes in diabetic mice
Yoshiro Maezawa1, Koutaro Yokote, Kiriko Sonezaki
1Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
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.
Insights
C-peptide treatment reduced albuminuria and suppressed early glomerular changes in a mouse model of type 1 diabetes. These effects are partly mediated by C-peptide
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- C-peptide shows promise in ameliorating diabetes-related kidney damage.
- Type 1 diabetes can lead to significant functional and structural renal alterations.
Purpose of the Study:
- To investigate the molecular mechanisms of C-peptide in early diabetic nephropathy.
- To assess C-peptide's impact on glomerular changes in a type 1 diabetes mouse model.
Main Methods:
- Streptozotocin-induced diabetic mice received C-peptide treatment.
- Urinary albumin excretion was measured via ELISA.
- Glomerular mRNA expression of TGF-beta1 and type IV collagen was quantified using real-time PCR.
Main Results:
- C-peptide significantly decreased urinary albumin excretion.
- C-peptide treatment inhibited the upregulation of alpha3IV collagen and TGF-beta1 in glomeruli.
- In vitro, C-peptide inhibited TGF-beta-induced type IV collagen upregulation in podocytes, involving the ERK pathway.
Conclusions:
- C-peptide effectively suppresses key early glomerular changes in experimental diabetes.
- The protective effects of C-peptide involve modulation of the TGF-beta signaling pathway in glomerular podocytes.
