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Metal-activated C-peptide facilitates glucose clearance and the release of a nitric oxide stimulus via the GLUT1 transporter.

Abstract：

AIMS/HYPOTHESIS:Proinsulin C-peptide has been implicated in reducing complications associated with diabetes and also in improving blood flow. We hypothesised that incubation of erythrocytes with C-peptide would improve the ability of these cells to release ATP, a stimulus for nitric oxide production. METHODS:Erythrocytes obtained from rabbits (n = 11) and both healthy and type 2 diabetic humans (n = 7) were incubated with C-peptide in the absence and presence of Fe2+ and Cr3+, and the resulting ATP release was measured via chemiluminescence. This release was also measured in the presence and absence of phloretin, an inhibitor of GLUT1, and also of mannose, a glycolysis inhibitor. To determine glucose transport, 14C-labelled glucose was added to erythrocytes in the presence and absence of the C-peptide-metal complex and the aforementioned inhibitors. RESULTS:The release of ATP from the erythrocytes of patients with diabetes increased from 64 +/- 13 to 260 +/- 39 nmol/l upon incubation of the cells in C-peptide. The C-peptide activity was dependent upon binding to Fe2+, which was extended upon binding to Cr3+. The increase in ATP release from the erythrocytes is due to metal-activated C-peptide stimulation of glucose transfer into the erythrocytes via the GLUT1 transporter. In the presence of C-peptide complexed to Cr3+, the amount of glucose transferred into the erythrocyte increased by 31%. CONCLUSIONS/INTERPRETATION:When complexed to Fe2+ or Cr3+, C-peptide has the ability to promote ATP release from erythrocytes. This release is due to an increase in glucose transport through GLUT1.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Meyer JA,Froelich JM,Reid GE,Karunarathne WK,Spence DM

doi

10.1007/s00125-007-0853-3

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

175-82

issue

1

eissn

0012-186X

issn

1432-0428

journal_volume

51

pub_type

杂志文章

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