title: Co-culture of clonal beta cells with GLP-1 and glucagon-secreting cell line impacts on beta cell insulin secretion, proliferation and susceptibility to cytotoxins.
abstract: We investigated the direct effects on insulin releasing MIN6 cells of chronic exposure to GLP-1, glucagon or a combination of both peptides secreted from GLUTag L-cell and αTC1.9 alpha-cell lines in co-culture. MIN6, GLUTag and αTC1.9 cell lines exhibited high cellular hormone content and release of insulin, GLP-1 and glucagon, respectively. Co-culture of MIN6 cells with GLUTag cells significantly increased cellular insulin content, beta-cell proliferation, insulin secretory responses to a range of established secretogogues and afforded protection against exposure cytotoxic concentrations of glucose, lipid, streptozotocin or cytokines. Benefits of co-culture of MIN6 cells with αTC1.9 alphacells were limited to enhanced beta-cell proliferation with marginal positive actions on both insulin secretion and cellular protection. In contrast, co-culture of MIN6 with GLUTag cells plus αTC1.9 cells, markedly enhanced both insulin secretory responses and protection against beta-cell toxins compared with co-culture with GLUTag cells alone. These data indicate important long-term effects of conjoint GLP-1 and glucagon exposure on beta-cell function. This illustrates the possible functional significance of alpha-cell GLP-1 production as well as direct beneficial effects of dual agonism at beta-cell GLP-1 and glucagon receptors.
authors.affiliation: SAAD Centre for Pharmacy & Diabetes, University of Ulster, Coleraine, Northern Ireland, UK.
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Green
authors.affiliation: SAAD Centre for Pharmacy & Diabetes, University of Ulster, Coleraine, Northern Ireland, UK. Electronic address: s.vasu@outlook.com.
authors.forename: Srividya
authors.initials: S
authors.lastname: Vasu
authors.affiliation: SAAD Centre for Pharmacy & Diabetes, University of Ulster, Coleraine, Northern Ireland, UK.
authors.forename: R Charlotte
authors.initials: RC
authors.lastname: Moffett
authors.affiliation: SAAD Centre for Pharmacy & Diabetes, University of Ulster, Coleraine, Northern Ireland, UK.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D018920:Coculture Techniques; D003603:Cytotoxins / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice
chemical_list: D003603:Cytotoxins; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
keywords: GLP-1; GLUTag; Glucagon; MIN6; αTC1.9