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I . In three separate experiments, four groups of five to eight young male rats were fed either (i) a high-protein diet, for which the net dietaryprotein : totalmetabolizableenergyratio ( N D~ : E) was 0.1 (HP diet); or (ii) a low-protein diet, for which N D~: E was 0.04 (LP diet). In both these groups, food intake was ad lib. In group (iii) the HP diet was given in an amount approximately equal to that taken by the LP group fed ad lib. (HP-restricted). In group (iv) rats were fasted for 48 h after receiving the H P diet (HP-fasted). Each experiment lasted 4 weeks.2. In the LP and HP-restricted groups, food intake was about 50% of that of the HP rats, while body-weight, after 4 weeks on diet was about 35 % and 5 5 yo of that of HP rats, for L P and HP-restricted respectively. Both groups of malnourished rats gained some weight during the experiment. 3. Measurements of oral glucose tolerance and plasma insulin levels were made in the fourth week. LP and HP-restricted rats both showed low fasting insulin levels and low insulin to glucose ratios during the glucose tolerance tests; the LP rats were more seriously affected.4. At the end of the fourth week the rats were killed and blood, liver and gastrocnemius muscle were analysed. LP rats showed specifically and consistently low values for haemoglobin and plasma protein concentration, and low activities of hepatic glucose-6-phosphatase (EC 3 , I . 3.9) and of alanine aminotransferase (EC 2.6. I . 2) in liver and muscle. The activity of hepatic aspartate aminotransferase (ECz. 6. I . I ) was, if anything, increased. The plasma amino acid concentrations and ratios showed a specific fall in branched-chain amino acids. Liver fat concentration was consistently elevated. The HP-restricted rats had normal values for haemoglobin, plasma protein and liver fat, and near-normal values for plasma amino acids. Hepatic alanine aminotransferase showed increased activity compared with H P rats, but muscle alanine aminotransferase showed reduced activity. The HP-fasted rats had increased haemoglobin, plasma protein and liver fat concentration, and very low liver glycogen concentrations. Hepatic alanine aminotransferase activity was elevated. Plasma alanine concentration was specifically reduced. .The results are consistent with suppression of gluconeogenesis, liver dysfunction and essential amino aciddeprivation in LP rats. These biochemical changes found in rats on a low intake of a diet of low proteinand high carbohydratevalue are similar to those found in kwashiorkor. An equally low intake of a diet of good protein value (HP-restricted) led to marginally better growth, accompanied by biochemical signs of increased gluconeogenesis, analogous to those reported for nutritional marasmus. This nutritional state was not biochemically identical with that of acute fasting.6. The results are discussed in terms of the consistency of the rat model, and its contribution to understanding biochemical changes found in infant malnutrition.

Severe protein-calorie deficiency resembling human syndromes (e.g., marasmus and kwashiorkor) has been produced in young pigs by manipulation of dietary protein and carbohydrate levels. These animals show impaired glucose tolerance; increased insulin sensitivity, including hypoglycemia nonresponsiveness; accumulation of glycogen in the liver and deficiency of hepatic glucose-6-phosphatase; normal or raised excretion of urinary corticosteroids. Tissue water content is elevated but fat accumulates only in animals receiving extra carbohydrate. It is suggested that a deficiency of insulin and of thyroid and growth hormones and a consequent relative excess of adrenocortical hormones is characteristic of severe protein-calorie deficiency in humans and experimental animals and explains many of the biochemical changes.

Littermate dogs were fed from weaning on high-protein diets (HP) or on dietswhich were adequate in calories but marginally deficient in protein (LP). The LP animals grew at a slightly retarded rate but showed no other outward abnormality. In the HP animals, intravenous glucose tolerance (K) increased steadily up to twelve months of age (K = 6) and then declined to the adult value (K = 4.7). These changes were accelerated and exaggerated in LP dogs so that, from seven months onwards, the K values for the LP dogs became progressively lower than those of their HP littermates. Although the LP diet was adequate for adult maintenance and other biochemical signs of proteincalorie deficiency were corrected in the adult, glucose tolerance remained impaired (mean K for HP adults = 4.7 and for LP adults = 3.3). In the LP dog decreasing glucose tolerance was associated with increasing resistance to exogenous insulin. During pregnancy, the HP animals showed an early increase in K followed by a progressive fall. The LP animals showed little change in K during pregnancy, but after lactation both glucose tolerance and sensitivity to insulin increased. Pups born to LP mothers showed signs of congenital malnutrition; they also showed greatly enhanced glucose tolerance in early life. Young dogs, whether fed HP or LP diets, showed rapid impairment of glucosetolerance when acutely infected with toxocara canis. The findings for dogs are compared with those reported in human diabetes mellitus.

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