C-peptide preserves the renal microvascular architecture in the streptozotocin-induced diabetic rat

Aims: C-peptide is renoprotective in type 1 diabetes, however, the mechanisms of its actions are not completely understood. We hypothesized that C-peptide attenuates diabetes-associated renal microvascular injury. Method: After 4 or 8 weeks of streptozotocin (STZ)-induced diabetes, rats received either vehicle or C-peptide in the presence of low or high doses of insulin. Urine albumin excretion (UAE) was measured prior to initiation of treatment (baseline) and 2 or 4 weeks after treatment (sacrifice). Glomerular hypertrophy, glomerular filtration rate (GFR) and renal microvascular density, quantified ex vivo by 3D micro-CT reconstruction, were measured at sacrifice. Results: In rats receiving low doses of insulin, treatment with C-peptide reduced HbA1c levels by 24%. In these rats, the 107% increase in UAE rate from baseline to sacrifice in vehicle-treated rats was largely prevented with C-peptide. C-peptide also reduced diabetes-associated glomerular hyperfiltration by 30%, glomerular hypertrophy by 22% and increased the density of microvessels between 0 and 500 mu m in diameter by an average of 31% compared with vehicle-treated groups. Similar renoprotective effects of C-peptide were observed in rats treated with higher doses of daily insulin, despite no differences in HbA1c levels. Conclusions: The study suggests that C-peptide is renoprotective by preserving the integrity of the renal microvasculature irrespective of glucose regulation. (C) 2013 Elsevier Inc. All rights reserved.