title: C-peptide and zinc delivery to erythrocytes requires the presence of albumin: implications in diabetes explored with a 3D-printed fluidic device.
abstract: People with type 1 diabetes (T1D) must administer insulin exogenously due to the destruction of their pancreatic β-cells. Endogenous insulin is stored in β-cell granules along with C-peptide, a 31 amino acid peptide that is secreted from these granules in amounts equal to insulin. Exogenous co-administration of C-peptide with insulin has proven to reduce diabetes-associated complications in animals and humans. The exact mechanism of C-peptide's beneficial effects after secretion from the β-cell granules is not completely understood, thus hindering its development as an exogenously administered hormone. Monitoring tissue-to-tissue communication using a 3D-printed microfluidic device revealed that zinc and C-peptide are being delivered to erythrocytes by albumin. Upon delivery, erythrocyte-derived ATP increased by >50%, as did endothelium-derived NO, which was measured downstream in the 3D-printed device. Our results suggest that hormone replacement therapy in diabetes may be improved by exogenous administration of a C-peptide ensemble that includes zinc and albumin.
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA. dspence@chemistry.msu.edu.
authors.forename: Yueli
authors.initials: Y
authors.lastname: Liu
authors.forename: Chengpeng
authors.initials: C
authors.lastname: Chen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Summers
authors.forename: Wathsala
authors.initials: W
authors.lastname: Medawala
authors.forename: Dana M
authors.initials: DM
authors.lastname: Spence
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000418:Albumins / Q000737:chemistry*; D000818:Animals; D002096:C-Peptide / Q000008:administration & dosage*; D002151:Calorimetry; D002450:Cell Communication; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000166:cytology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology; D056656:Lab-On-A-Chip Devices; D044085:Microfluidics; D010455:Peptides / Q000737:chemistry; D066330:Printing, Three-Dimensional; D051381:Rats; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D000418:Albumins; D002096:C-Peptide; D010455:Peptides; D000255:Adenosine Triphosphate; D015032:Zinc