01-03-2007 | For debate
C-peptide is a bioactive peptide
Published in: Diabetologia | Issue 3/2007
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During the past decade, reports from several laboratories have focused on the physiological effects of C-peptide. Experimental data and clinical studies suggest that that C-peptide is a biologically active peptide. Clinical studies show that C-peptide administration in type 1 diabetes patients, who lack the peptide, results in amelioration of diabetes-induced renal and nerve dysfunction. Molecular studies demonstrate binding to cell membranes, activation of intracellular signalling pathways, and specific end effects of importance for vascular endothelial function. These findings have prompted the hypothesis that C-peptide deficiency in type 1 diabetes may contribute to the development of microvascular complications, and that C-peptide replacement, together with regular insulin therapy, may be beneficial in the treatment or prevention of these complications. In the present article we argue the case in favour of C-peptide as a biologically active peptide based on in vivo data and in vitro findings, as summarised in Table 1.
Effect
|
Reference
|
---|---|
In vivo effects
|
|
Renal
|
|
Functional reserve ↑
|
[7]
|
Glomerular hyperfiltration ↓
|
|
Urinary albumin excretion ↓
|
[6]
|
Structural abnormalities ↓
|
[8]
|
Nerve
|
|
Conduction velocity ↑
|
|
Vibration perception ↑
|
[10]
|
Blood flow ↑
|
|
Na+/K+-ATPase activity ↑
|
|
Hyperalgesia ↓
|
[14]
|
Structural abnormalities ↓
|
|
Circulation
|
|
Muscle blood flow ↑
|
[16]
|
Skin blood flow ↑
|
[19]
|
Myocardial blood flow and contraction rate ↑
|
|
Myocardial ejection fraction ↑
|
|
QT interval ↓
|
|
In vitro effects
|
|
Membrane interaction
|
|
Specific binding in nanomolar range
|
|
Intracellular signalling
|
|
G-protein involvement
|
|
Intracellular Ca2+ ↑
|
|
PKC, MAPK and PI-3Kγ ↑
|
|
NFκB, PPARγ, Bcl2, c-Fos, ZEB ↑
|
|
End effects
|
|
eNOS activity and protein levels ↑
|
|
Na+/K+-ATPase activity and protein levels ↑
|
|
Cell growth ↑
|
[40]
|
Apoptosis ↓
|
|
Insulinomimetic effects
|
[32]
|
Anti-thrombotic effects
|
[21]
|
Other
|
|
Disaggregation of insulin hexamers
|
[41]
|