Effect of Sodium Linoleate Infusion on Plasma Free Fatty Acids, Glucose, Insulin, and Ketones in Unanesthetized Dogs

Abstract

By using a continuous-flow centrifuge to separate carotid artery blood into cells and plasma, sodium linoleate was infused into the jugular vein of five conscious dogs at a mean rate of 41.9 μEq. · kg.−1 · min−1 for ninety minutes without adverse side effects. Linoleate infusion quickly elevated plasma free fatty acid (FFA) levels to approximately 1.50 μEq./ml. and was accompanied by a rapid four- to sixfold increase in plasma immunoreactive insulin (IRI) which was sustained throughout the infusion. After thirty minutes of infusion, plasma glucose began to fall, ultimately declining 35 per cent from control levels. Plasma ketone levels rose to twice their control levels during linoleate infusion but were always less than 20 per cent of the ketone levels shown to be insulinogenic in dogs. Upon termination of the infusion, plasma FFA, IRI, and ketones fell quickly to control levels, while plasma glucose rose toward normal. The half-life of plasma linoleate, estimated from the infusion rate and the increment in plasma FFA during steady-state infusion, was 0.76 minute. This result, based on net flux, validates estimates based on tracer experiments. The similarity between the metabolic responses to linoleate infusion and those previously found to oleate suggests that these effects may be common to most physiologic long-chain FFA. Stimulation of insulin secretion by high levels of FFA could thus play a role in modulating lipolytic responses and changes in glucose metabolism accompanying such responses.

Insulin regulation of renal glucose metabolism in conscious dogs.

“…Moreover, the evidence that one quarter to one third of systemic glucose disappearance occurs in the kidney demonstrates the potential impact of changes in renal glucose uptake on overall glucose homeostasis. These observations require a more complicated model of glucoregulation, taking into consideration possible different effects on the kidney and liver of the large number of hormones (19)(20)(21) and substrates (22)(23)(24) known to affect systemic glucose metabolism. The approximate equality of renal glucose production and utilization, which results in modest to negligible net glucose balance, could be interpreted to indicate that the role of these two processes in whole body glucose homeostasis during the postabsorptive period is minimal.…”

Effect of fatty acids on glucose production and utilization in man.

“…Conversely, in normal man nicotinic acid administration causes a fall in plasma FFA concentrations but a rise in hepatic glucose output mediated by a decrease in plasma insulin and an increase in plasma glucagon levels (50). In general, FFA are insulin secretagogues (51,52), and their effect on plasma insulin levels counteracts any hyperglycemic action in vivo. In pancreatectomized dogs, however, reduction of circulating FFA by sodium nicotinate brings about a significant decrease in hepatic glucose production (48).…”