Minor role of fatty acid for mitochondial metabolism during insulin secretion
Aims: An appropriate insulin secretion by pancreatic beta-cells is necessary to maintain glucose homeostasis. In these cells a rise in plasma glucose results in an increased metabolism and an elevated cytoplasmic ATP/ADP ratio that finally triggers insulin granule exocytosis. In addition to this triggering pathway one or more amplifying pathways – activated by amino acids or fatty acid – enhance secretion by promoting insulin granule recruitment to, and priming at, the plasma membrane. The aim of this study was to clarify to which extend fatty acids increase insulin secretion via mitochondrial respiratory activity.
Methods: To study the impact of fatty acids on insulin secretion we isolated islets of Langerhans from mice and exposed them to glucose and fatty acids to determine insulin secretion as well as oxygen consumption rate with a Seahorse XF24 – 3 extracellular flux analyzer.
Results: Treatment of isolated islets with glucose (20 mM) increased insulin secretion 2.4 fold, whereas the additional stimulation with palmitate increased insulin release 10.6 fold. The coupling efficiency increased form 0.42 ± 0.04 to 0.67 ± 0.03 in response to glucose treatment, whereas the combination of glucose plus palmitate raised coupling efficiancy to 0.70 ± 0.03, indicating that the capacity of the respiratory activity for ATP production is not strongly elevated by fatty acids.
Conclusion: Our data clearly demonstrate that fatty acid-induced insulin secretion is only negligibly mediated by the mitochondrial activity, supporting the important role of an amplifying pathway.