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Arachidonic acid, palmitic acid and glucose are important for the modulation of clonal pancreatic beta-cell insulin secretion, growth and functional integrity.
- Source :
-
Clinical science (London, England : 1979) [Clin Sci (Lond)] 2004 Feb; Vol. 106 (2), pp. 191-9. - Publication Year :
- 2004
-
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.
- Subjects :
- Alanine metabolism
Ammonia analysis
Apoptosis drug effects
Cell Division drug effects
Cell Line
Glutamine metabolism
Humans
Insulin Secretion
Islets of Langerhans drug effects
Nitrites analysis
Triglycerides analysis
Arachidonic Acid pharmacology
Glucose metabolism
Insulin metabolism
Islets of Langerhans metabolism
Palmitic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0143-5221
- Volume :
- 106
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical science (London, England : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 14561212
- Full Text :
- https://doi.org/10.1042/CS20030261