Reactome | Intracellular metabolism of fatty acids regulates insulin secretion

Intracellular metabolism of fatty acids regulates insulin secretion

Stable Identifier

R-HSA-434313

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Intracellular metabolism of fatty acids regulates insulin secretion

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Fatty acids augment the glucose triggered secretion of insulin through two mechanisms: activation of FFAR1 (GPR40) and intracellular metabolism of fatty acids. Fatty acids are transported into the cell by CD36 (FAT) (Noushmehr et al. 2005) and metabolized by ligation to coenzyme A (Ansari et al. 2017), transport into mitochondria, and beta oxidation which generates ATP. The ATP increases the intracellular ratio of ATP:ADP and thereby closes potassium channels (K(ATP) channels) at the plasma membrane (reviewed in Acosta-Montano and Garcia-Gonzalez 2018). The enzymes that metabolize fatty acids in beta cells also metabolize fatty acids in other tissues however their combinations and subcellular locations may differ.

Literature References

PubMed ID	Title	Journal	Year
15677505	Fatty acid translocase (FAT/CD36) is localized on insulin-containing granules in human pancreatic beta-cells and mediates fatty acid effects on insulin secretion Doria, A, Noushmehr, H, Wawrowsky, KA, Farilla, L, Mlynarski, W, D'Amico, E, Abumrad, NA, Hui, H, Perfetti, R	Diabetes	2005
29565831	Effects of Dietary Fatty Acids in Pancreatic Beta Cell Metabolism, Implications in Homeostasis García-González, V, Acosta-Montaño, P	Nutrients	2018
28193492	Characterization of Acyl-CoA synthetase isoforms in pancreatic beta cells: Gene silencing shows participation of ACSL3 and ACSL4 in insulin secretion Stoker, SW, Ansari, IH, MacDonald, MJ, Fernandez, LA, Kendrick, MA, Ntambi, JM, Zitur, LJ, Longacre, MJ, O'Neill, LM	Arch. Biochem. Biophys.	2017