Studies on the carbohydrate metabolism of sheep. VIII. Hypoglycaemia and hyperketonaemia in undernourished and fasted pregnant ewes

Abstract

Relationships between blood levels of glucose, ketone bodies, volatile fatty acids (V.F.X.), and citrate have been studied in ewes fed on a submaintenance diet of wheaten chaff during the last 5 weeks of pregnancy. Pre-feeding levels, changes during S hr after feeding, and changes during fasting were studied. Pre-feeding hypoglycaemia was consistently more severe and the post'-prandial increase in blood glucose was less in ewes carrying twins than in ewes carrying single lambs. Blood citrate consistently increased after feeding, the magnitude of the increase depending on the extent of the increase in blood glucose. Mean citrate levels after feeding were highly correlated with mean glucose levels, which suggested that blood citrate reflected the activity of the tricarboxylic acid cycle in tissues. Pre-feeding ketone levels tended to vary inversely as blood glucose when hyperlietonaemia was moderate (less than 20 mg per cent. ketones) hut the correlation disappeared v-hen hyperketonaemia was severe (20-53 mg per cent.). When glucose increased appreciably after feeding, ketones usually declined and V.F.A. levels were normal, but when the increase in glucose was small and levels remained below 30 mg per cent. after feeding, ketone levels often did not change and V.F.A. levels were high. Mean values for ketones over a period of 8 hr after feeding were highly correlated with mean values for V.F.A. over a wide range. This can be explained on the basis of present knowledge of the metabolism of the acetyl-coenzyme A (acetyl- Co4) derived from absorbed acetate and from oxidation of higher fatty acids; it is suggested that the oxidation of acetyl-CoA is impaired as a result of depression of tricarboxylic acid cycle activity. During fasting, blood ketones varied inversely with glucose, but very high ketone levels (above 30 mg per cent.) were probably not due simply to the hypoglycaemia. The hypothesis is advanced that an excess of circulating hydrocortisone further depressed acetyl-CoA metabolism. The apparent correlations between blood glucose and ketones would then be due largely to the fact that the magnitude of the adrenal response, at any particular time in these experiments, was a function of the severity of hypoglycaemia and of the period during which it was previously maintained.