Abstract
Free fatty acid (FFA) is usually increased in the sera of poorly controlled diabetic patients and its undesirable actions on glucose metabolism are reported. In the present study, the effect of FFA on insulin biosynthesis was investigated using isolated rat islets in vitro. Palmitic acid (PA) decreased insulin biosynthesis during the incubation of islets in the presence of 11 mM glucose in a dose and time related manner. Exposure of islets to 1.0 mM PA for 1 hour or 4 hours incubation suppressed insulin biosynthesis by 40 %. This inhibitory effect of PA was disappeared after eliminating PA from the incubation medium. To evaluate the effect of PA on preproinsulin transcription, the content of insulin mRNA in the incubated islets was measured by Northern blot analysis. PA did not affect insulin mRNA content during the 4 hours incubation period, suggesting that PA acts on the translational process of insulin synthesis. To further assess the mechanisms by which PA inhibits the insulin biosynthesis, the effect of PA on the contents of glucose transporter (GLUT2) protein and glucokinase protein were determined by immunoblot analysis. GLUT2 protein content did not change by addition of PA, however, the glucokinase protein content decreased about half fold. In agreement with this result, glucokinase activity reduced also about half fold by addition of PA. In conclusion, FFA suppresses glucose-induced insulin biosynthesis at the translational process partly mediated through decreased glucokinase activity.
