1. Ketone-body utilization in fed and starved adult and suckling rats has been investigated by measuring arterio-venous differences across the brain. Venous blood was collected from the confluence of sinuses and arterial blood from the femoral artery in adult rats and by cardiac puncture in suckling rats. 2. During starvation the arterio-venous difference of ketone bodies increased in proportion to their concentrations in the blood and reached a value of 0.16mm at 48h. At a given concentration of the respective ketone bodies the arterio-venous differences of acetoacetate were about twice those of 3-hydroxybutyrate. 3. Fed rats in which the concentrations of ketone bodies were raised by intravenous infusion of sodium acetoacetate had the same arterio-venous differences as starved rats at corresponding ketone-body concentrations. Thus the ability of the rat brain to utilize ketone bodies is independent of the nutritional state. 4. The concentrations of glucose, acetoacetate and 3-hydroxybutyrate were much lower in the brain than in the arterial blood. The measured (blood concentration)/(brain concentration) ratio was 4.4 for glucose, 4.5 for acetoacetate and 8.1 for 3-hydroxybutyrate in 48h-starved rats. 5. The mean arterio-venous difference of glucose across the brain was 0.51mm in fed rats and 0.43mm in 96h-starved rats. 6. Conversion of glucose into lactate rose from negligible values in the fed state to 0.2mm after 48h starvation and decreased to zero after 96h starvation. 7. In 16-22-day-old suckling rats the arterio-venous differences of ketone bodies across the brain were also proportional to the ketone-body concentration, but they were about 3-4 times greater than in adult rats at the same blood ketone-body concentration. 8. Arterio-venous differences of glucose were about the same in adult and suckling rats. 9. The brain of fed suckling rats formed more lactate from glucose than fed adult rats. 10. The results indicate that ketone bodies are major metabolic fuels of the brain of the suckling rat under normal conditions.

SUMMARY In the 13 years since hepatic glycogen synthetase deficiency was first described in identical twins no further cases seem to have been observed. We report a child who had suffered from occasional morning convulsions since the age of 7. Three 24-hour metabolic profiles showed fasting hypoglycaemia, hyperketonaemia, but normal lactate. Hyperglycaemia and hyperlactataemia occurred after meals. Glucagon caused a rise in glucose 3 hours after a meal with a fall in lactate and alanine; no effect of glucagon was seen after a 12-hour fast. Normal increments in glucose followed oral galactose or alanine. Liver and abdominal wall muscle biopsies were taken. Glycogen content was subnormal in liver but normal in muscle. Glycogen synthetase (EC 2.4

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1. The metabolic and hormonal responses to intravenous glucose (0.5 g/kg body wt.) were studied in ten normal subjects and thirteen patients with active chronic hepatitis. Untreated patients showed a decreased initial insulin response and glucose intolerance (KG, 0.89 fO-lO%/min compared with 2*34+0*24%/min), together with a paradoxical rise in growth hormone.2. Fasting blood lactate and pyruvate were normal but both metabolites showed a diminished rise after glucose. The rate of rise of lactate was directly related to initial insulin secretion in both hepatitis subjects and controls.3. Fasting blood ketone bodies, blood glycerol, plasma triglycerides and free fatty acids were all significantly elevated in the patient group. Results were similar to those found in mild diabetes mellitus.4. In two patients with a more severe cirrhosis fasting values of serum insulin, growth hormone, blood lactate, pyruvate and glycerol were raised. 5. After corticosteroid therapy hyperinsulinism was found together with a return towards normal of glucose tolerance (KG, 1.49 +O.lO%/min), ketone bodies, free fatty acids and triglycerides ; blood glycerol remained elevated and lactate response to glucose was excessive.6. It is suggested that in active chronic hepatitis there might be pancreatic dysfunction on an autoimmune basis.

1. Sepsis induced by caecal ligation and puncture increased the rates of hepatic cholesterogenesis and fatty acid synthesis in vivo compared with sham-operated rats. These changes were accompanied by higher concentrations of lactate and pyruvate in blood and liver and an increase in plasma insulin. 2. The total activity of hydroxymethylglutarylcoenzyme A (HMG-CoA) reductase (EC 1.1.1.88) in liver was increased by sepsis, but there was no significant change in the expressed activity. Short-term insulin deficiency (induced by mannoheptulose or streptozotocin) decreased the rates of cholesterogenesis and fatty acid synthesis in livers of septic rats but did not alter the expressed/total activity of HMG-CoA reductase. 3. It is concluded that the increased rate of hepatic cholesterogenesis in septic rats is in part a result of the higher plasma insulin, the hormone acting to maintain the total activity of HMG-CoA reductase and to stimulate a step before the formation of HMG-CoA. 4. These changes may contribute to the hypertriacyl-glycerolaemia associated with sepsis.