title: Arachidonic acid, palmitic acid and glucose are important for the modulation of clonal pancreatic beta-cell insulin secretion, growth and functional integrity.
abstract: Insulin-resistant states such as obesity can result in an increase in the function and mass of pancreatic beta-cells, so that insulin secretion is up-regulated and Type II diabetes does not develop. However, expansion of beta-cell mass is not indefinite and may well decrease with time. Changes in circulating concentrations of nutritional factors, such as fatty acids and/or glucose, may lead to a reduction in beta-cell mass in vivo. Few previous studies have attempted to explore the interplay between glucose, amino acids and fatty acids with respect to beta-cell mass and functional integrity. In the present study, we demonstrate that culture of clonal BRIN-BD11 cells for 24 h with the polyunsaturated fatty acid arachidonic acid (AA) increased beta-cell proliferation and enhanced alanine-stimulated insulin secretion. These effects of AA were associated with significant decreases in the cellular consumption of D-glucose and L-alanine as well as decreased rates of production of nitric oxide and ammonia. Conversely 24 h exposure to the saturated fatty acid palmitic acid (PA) was found to decrease beta-cell viability (by increasing apoptosis), increase the intracellular concentration of triacylglycerol (triglyceride), while inhibiting alanine-stimulated insulin secretion. These effects of PA were associated with significant increases in D-glucose and L-glutamine consumption as well as nitric oxide and ammonia production. However, L-alanine consumption was decreased in the presence of PA. The effects of AA, but not PA, were additionally dependent on glucose concentration. These studies indicate that AA may have a critical role in maintaining the appropriate mass and function of islet beta-cells by influencing rates of cell proliferation and insulin secretion. This regulatory effect may be compromised by high circulating levels of glucose and/or PA, both of which are elevated in Type II diabetes and may impact upon dysfunctional and apoptotic intracellular events in the beta-cell.
authors.affiliation: Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dixon
authors.forename: John
authors.initials: J
authors.lastname: Nolan
authors.forename: Neville H
authors.initials: NH
authors.lastname: McClenaghan
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
authors.forename: Philip
authors.initials: P
authors.lastname: Newsholme
mesh_terms: D000409:Alanine / Q000378:metabolism; D000641:Ammonia / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis; D019308:Palmitic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000032:analysis
chemical_list: D007328:Insulin; D009573:Nitrites; D014280:Triglycerides; D005973:Glutamine; D016718:Arachidonic Acid; D019308:Palmitic Acid; D000641:Ammonia; D005947:Glucose; D000409:Alanine