Effects of synthetic rat C-peptide in normal and diabetic rats

Wójcikowski, Cz.; Maier, V.; Dominiak, K; Rd, Fussgänger; Pfeiffer, E. F.

doi:10.1007/bf00279945

Cited by 38 publications

(26 citation statements)

References 8 publications

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“…In diabetic rats, supra-physiological concentrations of C-peptide prolonged the hypoglycaemic actions of insulin [46] and, later, using the euglycaemic clamp technique in STZ (streptozotocin)-induced diabetic rats, physiological concentrations of rat C-peptide were found to significantly augment the disposal and metabolic clearance rates for glucose [47]. This result was largely blocked by the NOS inhibitor l-NMMA (N Gmonomethyl-l-arginine), suggesting that these actions of C-peptide were mediated by NO.…”

Section: C-peptide and Glucose Handlingmentioning

confidence: 99%

Cellular and physiological effects of C-peptide

Hills

Brunskill

2009

Clinical Science

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In recent years, accumulating evidence indicates a biological function for proinsulin C-peptide. These results challenge the traditional view that C-peptide is essentially inert and only useful as a surrogate marker of insulin release. Accordingly, it is now clear that C-peptide binds with high affinity to cell membranes, probably to a pertussis-toxin-sensitive G-protein-coupled receptor. Subsequently, multiple signalling pathways are potently and dose-dependently activated in multiple cell types by C-peptide with the resulting activation of gene transcription and altered cell phenotype. In diabetic animals and Type 1 diabetic patients, short-term studies indicate that C-peptide also enhances glucose disposal and metabolic control. Furthermore, results derived from animal models and clinical studies in Type 1 diabetic patients suggest a salutary effect of C-peptide in the prevention and amelioration of diabetic nephropathy and neuropathy. Therefore a picture of Type 1 diabetes as a dual-hormone-deficiency disease is developing, suggesting that the replacement of C-peptide alongside insulin should be considered in its management.

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Section: C-peptide and Glucose Handlingmentioning

confidence: 99%

Cellular and physiological effects of C-peptide

Hills

Brunskill

2009

Clinical Science

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“…The early augmented glomerular filtration may play a crucial role in the development of diabetic nephropathy, and inhibition of the diabetesinduced hyperfiltration have beneficial effects on delaying the progression of kidney damage 6 . C-peptide is secreted from the islets of Langerhans together with insulin in equimolar amounts, and has been shown to influence physiological processes 7 . Several studies have also shown renoprotective effects of exogenous C-peptide administration to patients with type-1 diabetes 8,9 , but also to animals with experimental insulinopenic diabetes 9,10 .…”

Section: Introductionmentioning

confidence: 99%

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

Stridh

Sällström

Fridén

et al. 2009

Advances in Experimental Medicine and Biology

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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.

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“…However, in the early 1980s, it was suggested that C-peptide may influence biological functions (59). Several recent studies have reported renoprotective effects of C-peptide when it is administered to patients with type 1 diabetes (13,19,20) and animal models of experimental insulinopenic diabetes (16,36,(47)(48)(49)51).…”

mentioning

confidence: 99%

Proinsulin C-peptide reduces diabetes-induced glomerular hyperfiltration via efferent arteriole dilation and inhibition of tubular sodium reabsorption

Nordquist

Brown

Fasching

et al. 2009

American Journal of Physiology-Renal Physiology

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C-peptide reduces diabetes-induced glomerular hyperfiltration in diabetic patients and experimental animal models. However, the mechanisms mediating the beneficial effect of C-peptide remain unclear. We investigated whether altered renal afferent-efferent arteriole tonus or alterations in tubular Na+ transport (T(Na)) in response to C-peptide administration mediate the reduction of diabetes-induced glomerular hyperfiltration. Glomerular filtration rate, filtration fraction, total and cortical renal blood flow, total kidney O2 consumption (QO2), T(Na), fractional Na+ and Li+ excretions, and tubular free-flow and stop-flow pressures were measured in anesthetized adult male normoglycemic and streptozotocin-diabetic Sprague-Dawley rats. The specific effect of C-peptide on transport-dependent QO2 was investigated in vitro in freshly isolated proximal tubular cells. C-peptide reduced glomerular filtration rate (-24%), stop-flow pressure (-8%), and filtration fraction (-17%) exclusively in diabetic rats without altering renal blood flow. Diabetic rats had higher baseline T(Na) (+40%), which was reduced by C-peptide. Similarly, C-peptide increased fractional Na+ (+80%) and Li+ (+47%) excretions only in the diabetic rats. None of these parameters was affected by vehicle treatments in either group. Baseline QO2 was 37% higher in proximal tubular cells from diabetic rats than controls and was normalized by C-peptide. C-peptide had no effect on ouabain-pretreated diabetic cells from diabetic rats. C-peptide reduced diabetes-induced hyperfiltration via a net dilation of the efferent arteriole and inhibition of tubular Na+ reabsorption, both potent regulators of the glomerular net filtration pressure. These findings provide new mechanistic insight into the beneficial effects of C-peptide on diabetic kidney function.

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Effects of synthetic rat C-peptide in normal and diabetic rats

Cited by 38 publications

References 8 publications

Cellular and physiological effects of C-peptide

Cellular and physiological effects of C-peptide

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

Proinsulin C-peptide reduces diabetes-induced glomerular hyperfiltration via efferent arteriole dilation and inhibition of tubular sodium reabsorption

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