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The ratio of C‐peptide to insulin is critical for low oxygen tension‐induced ATP release from human erythrocytes (RBCs)
Author(s) -
Richards Jennifer,
Stephenson Alan H.,
Ellsworth Mary L.,
Sprague Randy S.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.860.24
Subject(s) - insulin , peptide , chemistry , c peptide , medicine , endocrinology , biochemistry
Exposure to low oxygen tension (pO 2 ~ 20mmHg) stimulates ATP release from RBCs, allowing these cells to direct blood flow to areas of increased O 2 need. We showed that low pO 2 ‐induced ATP release from RBCs is inhibited by insulin at concentrations present in prediabetes contributing to defective vascular control. Here we investigated the hypothesis that C‐peptide, at physiological concentrations, attenuates the adverse effects of insulin on low pO 2 ‐induced ATP release from human RBCs. Although C‐peptide and insulin are co‐released at equimolar concentrations, due to differing clearance rates, they circulate at different concentrations. When insulin and C‐peptide were administered at a 1:1 ratio (ratio when released), low pO 2 ‐induced ATP release was not decreased (n=5). However, since this ratio is not present in vivo for extended periods, we tested additional ratios of C‐peptide to insulin: 6:1 and 4:1. We determined that a ratio of 6:1 (n=5) inhibits ATP release induced by low pO 2 . However, at 4:1, a ratio present physiologically in healthy humans, C‐peptide and insulin did not inhibit low pO 2 ‐induced ATP release (n=7). Our results indicate that the ratio of C‐peptide to insulin is important for low pO 2 ‐ induced ATP release from RBCs and suggest that co‐administration of C‐peptide with insulin could attenuate insulin‐induced adverse effects on microvascular perfusion. Supported by grants from the ADA and NIH.