Beside functional and structural changes in vascular biology,
alterations in the rheologic properties of blood cells
mainly determines to an impaired microvascular blood
flow in patients suffering from diabetes mellitus. Recent
investigations provide increasing evidence that impaired
C-peptide secretion in type 1 diabetic patients might contribute
to the development of microvascular complications.
C-peptide has been shown to stimulate endothelial
NO secretion by activation of the Ca2+calmodolin regulated
enzyme eNOS. NO himself has the potency to increase
cGMP levels in smooth muscle cells and to activate
Na+K+ATPase activity and therefore evolves numerous effects
in microvascular regulation. In type 1 diabetic patients,
supplementation of C-peptide was shown to improve endothelium
dependent vasodilatation in an NO-dependent
pathway in different vascular compartments. In addition,
it could be shown that C-peptide administration in type 1
diabetic patients, results in a redistribution of skin blood
flow by increasing nutritive capillary blood flow in favour
to subpapillary blood flow. Impaired Na+K+ATPase in another
feature of diabetes mellitus in many cell types and
is believed to be a pivotal regulator of various cell functions.
C-peptide supplementation has been shown to restore
Na+K+ATPase activity in different cell types during
in vitro and in vivo investigations. In type 1 diabetic patients,
C-peptide supplementation was shown to increase
erythrocyte Na+K+ATPase activity by about 100%. There
was found a linear relationship between plasma C-peptide
levels and erythrocyte Na+K+ATPase activity. In small
capillaries, microvascular blood flow is increasingly determined
by the rheologic properties of erythrocytes. Using laser-diffractoscopie a huge improvement in erythrocyte deformability
could be observed after C-peptide administration
in erythrocytes of type 1 diabetic patients. Inhibition
of the Na+K+ATPase by Obain completely abolished the
effect of C-peptide on erythrocyte deformability. In conclusion,
C-peptide improves microvascular function and blood
flow in type 1 diabetic patients by interfering with vascular
and rheological components of microvascular blood flow.
