Premium
The Cellular Response to C‐peptide is Dependent on the Concentration of Glucose and Insulin
Author(s) -
Rossiter Jackie Lee,
Kolar Grant R,
Yosten Gina LC
Publication year - 2017
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.31.1_supplement.715.3
Subject(s) - medicine , endocrinology , insulin , peptide , c peptide , receptor , basal (medicine) , beta cell , hek 293 cells , chemistry , islet , biology , biochemistry
The role of insulin in the regulation of blood glucose has been the subject of extensive research. Insulin and C‐peptide, a 31 amino acid peptide, are co‐produced and co‐secreted by pancreatic beta islet cells. In 2013, a candidate receptor for C‐peptide was identified by our group to be the G‐protein coupled receptor, GPR 146. On release the relative concentrations of insulin to C‐peptide are 1:1, however due to differences in sites and rates of catabolism, in plasma the relative ratios of insulin to C‐peptide are 1:5. There is a growing body of evidence to support a physiologic role for C‐peptide in the prevention of co‐morbidities associated with microvascular damage in individuals with diabetes. These co‐morbidities include increased incidence of cardiovascular disease, retinopathies, renal failure and poor wound healing. We hypothesized that the cellular response to C‐peptide is dependent on the relative concentrations of C‐peptide, glucose, and insulin. In this study, HEK293 cells were incubated with varying levels of glucose (40 mg/dl, 115mg/dl, or 450 mg/dl), C‐peptide (0, 0.1nM, 1.0nM, or 10nM), or insulin (0, 100pM, 1000pM, or 2000pM). HEK293 cell responses were evaluated by comparing relative levels of cFOS, GPR146, and insulin receptor (IR) mRNA expression. Incubation of HEK293 in high glucose with basal levels (0.1nM) of C‐peptide resulted in HEK293 activation as measured by cFOS mRNA. Basal (0.1nM) C‐peptide induces production of GPR146 mRNA in conditions of low and high glucose but had no significant effect in normal glucose conditions. However, for HEK293 cells incubated with basal C‐peptide and high glucose, the addition of insulin ameliorated cellular activation induced by C‐peptide. Thus, the cellular responses to C‐peptide were dependent on ambient levels of glucose and insulin. These findings have important implications for the development of C‐peptide based therapies. C‐peptide therapeutics may be of benefit in high glucose conditions, however those benefits may be confounded the presence of exogenous insulin that exceeds physiologic parameters of insulin to C‐peptide (1:5). Support or Funding Information HL121456