Dependence of the plasma triacylglycerol-lowering effect of fish oil on insulin replacement in streptozotocin diabetic rats.

Streptozotocin diabetic rats, with and without insulin replacement, and sham-injected controls were fed a high-fat (30% of energy) menhaden oil (MO) or corn oil (CO) diet for 2 weeks. After an overnight fast, plasma and livers were collected for analysis of insulin, glucose, triacylglycerol, cholesterol and glucose-6-phosphate dehydrogenase activity. Streptozotocin treatment resulted in decreased plasma insulin and elevated glucose. MO-feeding to insulin-replaced diabetic rats resulted in higher insulin and lower glucose levels compared to the respective CO-fed rats, suggesting decreased hepatic insulin extraction and greater peripheral utilization of glucose with MO. Plasma triacylglycerol and cholesterol, and hepatic glucose-6-phosphate dehydrogenase activity were reduced in MO-fed vs. CO-fed control rats. These effects of MO were prevented in the diabetic rats but were restored by insulin replacement. We conclude from our data that the presence of insulin is required to observe at least some of the effects of fish oil (FO). To explain our observations we propose that many of the effects of FO on hepatic metabolism are mediated by an inhibition of insulin action in the liver, thus providing a possible central mechanism for the regulation of hepatic lipid metabolism by dietary FO.