Effect of hypoglycemia on the brain free fatty acid level and the uptake of fatty acids by phospholipids.

The effect of hypoglycemia on the uptake of [1-14C]arachidonate and [1-14C]oleate into a synaptosomal and microsomal glycerophospholipids was investigated. In the presence of ATP, Mg2+ and CoA, rat brain synaptosomes and microsomes catalyze the transfer of arachidonate and oleate into glycerophospholipids. Arachidonate was mainly incorporated into phosphatidylinositol (PI) and phosphatidylcholine (PC), whereas oleate was incorporated into phosphatidylcholine and phosphatidylethanolamine (PE). Hypoglycemia was produced by intraperitoneal injection of 10 or 100 units of crystalline insulin per kg body weight. Two hours after injection the blood glucose level decreased to 10-20 mg%. The content of brain phospholipids was slightly decreased but the change was not statistically significant. The level of free fatty acids (FFA) was increased. More pronounced and reproducible changes were found when hypoglycemia was produced by injection of 100 units of insulin per/kg body weight. Changes in brain cortex were similar to those observed in microsomes and synaptosomes. Hypoglycemia affected the incorporation of arachidonic acid into glycerophospholipids of brain membranes. Uptake of [1-14C]arachidonate was decreased selectively by 50% (into phosphatidic acid/PA/) when hypoglycemia was produced by injection of 10 units of insulin per kg body weight. The higher dose of insulin 100 units per kg body weight produced a 20% inhibition of arachidonate incorporation into synaptosomal PI and a 13% decrease of incorporation into microsomal phosphatidylcholine. Incorporation of [1-14C]oleate into membrane phospholipids was not changed by hypoglycemic insult. It is proposed that the disturbances in fatty acid level, particularly arachidonate, and decreased uptake of arachidonic acid by synaptosomal glycerophospholipids may be responsible for alteration of membrane function and changes of synaptic processes.