Role of C‐Peptide in the Regulation of Microvascular Blood Flow

T Forst,B Wilhelm,A Pfützner,T Kunt,M M Weber

doi:10.1155/2008/176245

Abstract

During the recent years, the role of C-peptide, released from the pancreatic beta cell, in regulating microvascular blood flow, has received increasing attention. In type 1 diabetic patients, intravenous application of C-peptide in physiological concentrations was shown to increase microvascular blood flow, and to improve microvascular endothelial function and the endothelial release of NO. C-peptide was shown to impact microvascular blood flow by several interactive pathways, like stimulating Na+K+ATPase or the endothelial release of NO. There is increasing evidence, that in patients with declining beta cell function, the lack of C-peptide secretion might play a putative role in the development of microvascular blood flow abnormalities, which go beyond the effects of declining insulin secretion or increased blood glucose levels.

Highlights

Patients with diabetes mellitus type 1 present with an extensive risk for microvascular complications like retinopathy, nephropathy, and peripheral neuropathy
It is not possible to separate the beneficial effects of residual C-peptide secretion from those of residual insulin secretion, there is increasing evidence that C-peptide might play a putative role in the physiology of microvascular blood flow regulation
It is speculative to discuss the underlying mechanism based upon these results, but impaired Na+K+ATPase activity may contribute to the decrease in erythrocyte deformability by increasing the intracellular sodium concentration with subsequent intracellular accumulation of free calcium ions due to competition in transmembranous exchange [45]

Summary

INTRODUCTION

Patients with diabetes mellitus type 1 present with an extensive risk for microvascular complications like retinopathy, nephropathy, and peripheral neuropathy. NO elicits vasodilatation through stimulation of endothelial NO-synthase (eNOS), increasing the endothelial release of NO and subsequent activation of the guanylcyclase in the vascular smooth muscle cell [12, 17,18,19]. It was shown that C-peptide increases NO release from aortic endothelial cells by enhancing eNOS expression through an ERK-dependent transcriptional pathway. There are tissue specific differences in the regulations of Na+K+-ATPase activity, hyperglycemia and diabetes are predominantly characterized by a decrease in ouabain-sensitive Na+K+-ATPase activity This would result in an increase in intracellular calcium concentration and an increased vascular tone, promoting the development of vascular complications in diabetes mellitus. Intravenous infusion of C-peptide was found to improve erythrocyte Na+K+ATPase activity in type 1 diabetic patients [38]

EFFECT OF C-PEPTIDE ON RED CELL DEFORMABILITY

EFFECTS OF C-PEPTIDE ON MICROVASCULAR BLOOD FLOW

Findings

CONCLUSIONS