C-Peptide Normalizes Glomerular Filtration Rate in Hyperfiltrating Conscious Diabetic Rats

Abstract

Tubular electrolyte transport accounts for a major part of the oxygen consumed by the normal kidney. We have previously reported a close association between diabetes and increased oxygen usage, partly due to increased tubular electrolyte transport secondary to glomerular hyperfiltration during the early onset of diabetes. Several studies have shown that acute administration of C-peptide to diabetic rats with glomerular hyperfiltration results in normalized glomerular filtration rate (GFR). In this study, we validated a novel method for precise and repetitive GFR measurements in conscious rats and used C-peptide injection in diabetic rats for evaluation. First, GFR was determined in normoglycemic control rats before and after C-peptide administration. Thereafter, all rats were made diabetic by an i.v. streptozotocin injection. Fourteen days later, GFR was again determined before and after C-peptide administration. GFR was estimated from plasma clearance curves using a single bolus injection of FITC-inulin, followed by serial blood sampling over 155 min. FITC-inulin clearance was calculated using non-compartmental pharmacokinetic data analysis. Baseline GFR in normoglycemic controls was 2.10 +/- 0.18 ml/min, and was unaffected by C-peptide (2.23 +/- 0.14 ml/min). Diabetic rats had elevated GFR (3.06 +/- .034 ml/min), which was normalized by C-peptide (2.35 +/- 0.30 ml/min). In conclusion, the used method for estimation of GFR in conscious animals result in values that are in good agreement with those obtained from traditional GFR measurements on anaesthetized rats. However, multiple measurements from the same conscious subject can be obtained using this method. Furthermore, as previously shown on anaesthetized rats, C-peptide also normalizes GFR in hyperfiltrating conscious diabetic rats.

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

“…Those studies showed that C-peptide reduces UAE and glomerular hypertrophy and normalizes glomerular hyperfiltration via afferent arteriolar constriction and net dilation of the efferent arteriole (Huang et al 2002; Johansson et al 2000; Maezawa et al 2006; Nordquist et al 2009; Nordquist et al 2008; Samnegard et al 2005; Samnegard et al 2001; Stridh et al 2009). Data from the present study not only confirm that C-peptide is renoprotective in the STZ-induced diabetic rat via similar mechanisms, but also extends those observations by showing that administration of C-peptide slows the progression of the disease in animals with already elevated albuminuria.…”

C-Peptide: A New Mediator of Atherosclerosis in Diabetes

“…Moreover, improvements of endoneurial blood flow and axonal swelling have been also demonstrated by introduction of C-peptide [51]. In numerous studies of type 1 diabetes glomerular hyperfiltration, hypertrophy, and proteinuria have been reduced by C-peptide [13, 14, 52]. C-peptide treatment improves sensory nerve function in early stage of type 1 diabetic neuropathy [47].…”

Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db/db mice as a model of type 2 diabetes

“…Glomerular filtration rate in conscious mice Conscious GFR was measured by the single bolus injection method of FITC-inulin clearance [29]. Briefly, 2% FITC-inulin was dissolved in PBS and dialysed in PBS at 4°C overnight in a 1000 Da cut-off dialysis membrane (Spectra/Por 6 Membrane, Spectrum Laboratories, Rancho Dominguez, CA, USA).…”