Abstract
It is well known that free fatty acids (FFAs) play a central role in insulin resistance. However, increasing evidence suggests that they are also implicated in the control of pancreatic insulin secretion. Simultaneous exposure of pancreatic β-cells to high levels of glucose and to saturated FFAs results in a substantial increase in insulin release, whereas chronic exposure may lead to a desensitization and suppression of secretion. A source of fatty acid, either exogenous or endogenous, is necessary to support normal insulin secretion. A rapid increase in fatty acids potentiates glucose-stimulated secretion by increasing the concentration of fatty acyl-coenzyme A or complex lipids, which act indirectly by modulating key enzymes, such as protein kinase C, or directly by modulating the exocytotic machinery. Mathematical models including FFAs in controlling insulin secretion are devised. Finally, insulin secretion in a human model of very low-fat diet, the malabsorptive bariatric surgery for morbid obesity, is described.