Experimental diabetic ketoacidosis. Sequential changes of metabolic intermediates in blood, liver, cerebrospinal fluid and brain after acute insulin deprivation in the streptozotocin-diabetic rat

Abstract

Male rats rendered diabetic by the intravenous injection of streptozotocin (150mg/kg) were treated with a long-acting insulin for 1 week, then allowed to develop ketoacidosis. By using sampling techniques designed to avoid the use of anaesthesia and extended anoxic periods, sequential measurements of metabolic intermediates were made in blood, liver, cerebrospinal fluid and brain at 24h intervals after the last insulin injection. Measurements in blood and liver suggested a rapid increase in hepatic glycogenolysis and gluconeogenesis and peripheral-depot lipolysis between 24 and 48h after the last insulin injection, whereas blood and liver ketone-body and triglyceride concentrations rose more slowly. The changing metabolic patterns occurring with increasing time of insulin deprivation stress the importance of sequential compared with static measurements in experimental diabetes. Data are presented for brain metabolic intermediates in diabetic ketoacidosis, and support recent evidence that glucose plays a less important role in brain oxidative metabolism in ketotic states.