Effect of starvation and a protein diet on the amino acid metabolism enzyme activities of the organs of domestic fowl hatchlings

The activities of alanine and aspartate transaminases, adenylate deaminase, glutamine synthetase and glutamate and xanthine dehydrogenases have been measured in liver, yolk sac membrane, intestine and breast and leg muscle of domestic fowl hatchlings receiving for 3 or 5 days either a standard diet or hard boiled eggwhite as well as in 3 or 5 days starved animals. The patterns of activation of amino acid metabolism enzymes were fully comparable in protein-fed and starved groups with respect to fed controls; the differences with respect to the latter became more marked in 5- than in 3-days old chicks. In 5-days old chicks intestine alanine transaminase activity increased in parallel to that of liver in protein-fed animals but not in those starved, in agreement with an enhanced alanine transfer between both organs under this situation. Both, starvation and protein-feeding, induced a general decrease in the amino acid metabolizing ability of muscle. Glutamine (but not alanine) synthetizing capabilities were enhanced.     

Studies on cerebral energy metabolism during the course of galactose neurotoxicity in chicks

—At various times during a 2-day study, the levels of adenine nucleotides and selected glycolytic intermediates were determined in brains of chicks fed a diet containing d -galactose (40%, w/w). The levels of ATP and glucose 6-phosphate had decreased by 9 h after initiation of the diet, whereas those of fructose 1,6-diphosphate, 3-phosphoglycerate, l -α-glycerophosphate, and lactate were not reduced until after 18 h had elasped. Although glucose 1-phosphate was not appreciably affected, glucose and glycogen were depleted during the latter stages of the toxicity. The cerebral levels of 3′,5′-cyclic AMP and citrate did not differ significantly between the two dietary groups at 48 h. The changes in the levels of cerebral glycolytic intermediates and high-energy phosphates during ischemia indicated that the glycolytic rate was diminished in the chicks fed galactose and that high-energy phosphate compounds were depleted sooner than in controls. After intraperitoneal injection of [¹⁴C]glucose, the specific radioactivity and levels of glucose in the plasma from chicks fed either diet were similar, whereas they were significantly reduced in the brains from galactosefed animals. We suggest that galactose interferes with the uptake of glucose into the brain and that this mechanism may be an important factor in d -galactose-induced neurotoxicity in the chick.     

Influence of dietary composition on gluconeogenesis from L-(U-14C)glutamate in rainbow trout (Salmo gairdneri)

The effect of dietary composition (high-protein, high-carbohydrate and high-fat diets) and starvation on in totum gluconeogenesis from L-(U-14C)glutamate was studied in the rainbow trout. High-fat and high-carbohydrate diets produced a significant hyperglycaemia. Lower blood glucose values were obtained in trout fed on a high-protein diet. Liver glycogen levels were significantly lower in trout fed on carbohydrate-free diets (high-protein and high-fat diets) and in starved fish. Gluconeogenesis from L-(U-14C)glutamate was markedly reduced in fish given the high-carbohydrate diet and significantly enhanced in starved fish. Radioactive liver glycogen was higher in starved fish, although the amount of radioactivity incorporated into glycogen was very low.     

Glycogen synthesis by hepatocytes from diabetic rats.

Hepatocytes prepared from streptozotocin- and alloxan-diabetic rats starved for 24 h contain 0.5--2% wet wt. of glycogen. Glycogen synthesis in the hepatocytes from such rats, after prior depletion of the glycogen by glucagon injection, was studied. As distinct from cells from normal animals, there was no glycogen synthesis from glucose as sole substrate, even at concentrations of 60 mM. When supplied with glucose, a gluconeogenic precursor (lactate, dihydroxyacetone or fructose), and with glutamine there was concurrent synthesis of glucose and of glycogen. Without glutamine there was little or no glycogen synthesis. The rate of glycogen formation was in the same range as for cells from control rats. Glutamine addition markedly activated glycogen synthase in cells of starved diabetic rats, but there was no effect on phosphorylase. We obtained very little synthesis of glycogen with hepatocytes from fed diabetic rats, whereas with normal animals, synthesis by such cells equals or exceeds that obtained from starved rats. The conversion of synthase b (inactive) into the active form was studied in rat liver homogenates. The activation of the synthase in cells from starved diabetic rats is somewhat less than that from normal animals, but that from fed diabetic rats is markedly decreased compared with that in livers of fed control animals or that of starved diabetic animals.     

Effects of a cafeteria diet and starvation of global 14C(U)-glucose disposal

The label distribution in control and cafeteria-diet fed rats, either in basal conditions or after 24 hours of food deprivation, 10 minutes after the i.v. injection of carrier-free D-14C-(U)-glucose, has been studied. The radioactivity recovered in the different fractions of liver, kidney, heart, striated muscle and white adipose tissue showed comparable patterns of change with starvation in both dietary groups. Most of the radioactivity was found in the free amino acid fraction as well as in proteins, with significant proportions also in lipid and liver glycogen. However, most of the label was lost due to its oxidation, remaining in the combined indicated tissues 10-20% of the injected label. On the whole, cafeteria rats consumed more glucose than controls, the lowest oxidation corresponding to the starved-control group. The amount of glucose oxidized by cafeteria rats was actually comparable to that of fed controls. The availability of other energetic sources--i.e. lipid--allows for an increased glucose utilization in cafeteria rats, even in the starved state.     

Cod and soy proteins compared with casein improve glucose tolerance and insulin sensitivity in rats

The aim of the present study was to determine the effects of feeding various dietary proteins on insulin sensitivity and glucose tolerance in rats. Male Wistar rats were fed for 28 days with isoenergetic diets containing either casein, soy protein, or cod protein. Cod protein-fed and soy protein-fed rats had lower fasting plasma glucose and insulin concentrations compared with casein-fed animals. After intravenous glucose bolus, cod protein- and soy protein-fed rats induced lower incremental areas under glucose curves compared with casein-fed animals. Improved peripheral insulin sensitivity was confirmed by higher glucose disposal rates in cod protein- and soy protein-fed rats (15.2 +/- 0.3 and 13.9 +/- 0.6 mg. kg(-1). min(-1), respectively) compared with casein-fed animals (6.5 +/- 0.7 mg. kg(-1). min(-1), P < 0.05). Moreover, test meal experiments revealed that, in the postprandial state, the lower plasma insulin concentrations in cod protein- and soy protein-fed animals could be also due to decreased pancreatic insulin release and increased hepatic insulin removal. In conclusion, the metabolic responses to three common dietary proteins indicate that cod and soy proteins, when compared with casein, improve fasting glucose tolerance and peripheral insulin sensitivity in rats.     

Carbohydrate metabolism of the isolated perfused liver of normal and genetically obese–hyperglycaemic (ob/ob) mice

1. A technique for perfusion of the mouse liver has been developed, and aspects of carbohydrate metabolism have been investigated in the perfused liver of normal and genetically obese mice, homozygous for the recessive gene ob. 2. Rates of gluconeogenesis in perfused mouse liver were faster than those reported for slices of mouse liver, particularly from lactate and pyruvate. 3. The rate of glycogen breakdown to glucose, but not to lactate, was faster in liver from fed obese mice. 4. The capacity for glycogen synthesis from glucose was enhanced in liver from 20h-starved obese mice. 5. The capacity for gluconeogenesis from a number of substrates was not significantly altered in livers from fed or starved obese mice when compared with that of lean mice. 6. These results suggest that the liver contributes to the hyperglycaemia of the obese mice by increased glycogenolysis, and that liver glycogen in obese mice is maintained by synthesis from dietary glucose.     

Stimulation by vasopressin of glycogen breakdown and gluconeogenesis in the perfused rat liver

1. Vasopressin (anti-diuretic hormone, [8-arginine]vasopressin) stimulated the breakdown of glycogen in perfused livers of fed rats, at concentrations (50-600muunits/ml) that have been reported in the blood of intact rats, especially during acute haemorrhagic shock. 2. In perfused livers from starved rats, vasopressin (30-150muunits/ml) stimulated gluconeogenesis from a mixture of lactate, pyruvate and glycerol. 3. Vasopressin prevented accumulation of liver glycogen in the perfused liver of starved rats, or in starved intact rats. 4. The action of vasopressin on hepatic carbohydrate metabolism thus resembles that of glucagon; the minimum effective circulating concentrations of these hormones are of the same order (100pg/ml). 5. The stimulation of hepatic glucose output by vasopressin is discussed in connexion with the release of glucose and water from the liver.     

The effect of starvation and starvation followed by feeding on enzyme activity and the metabolism of [U-14C]glucose in liver from growing chicks

1. The conversion of [U-(14)C]glucose into carbon dioxide, cholesterol and fatty acids in liver slices and the activities of ;malic' enzyme, citrate-cleavage enzyme, NADP-linked isocitrate dehydrogenase and hexose monophosphate-shunt dehydrogenases in the soluble fraction of homogenates of liver were measured in chicks that were starved or starved then fed. 2. In newly hatched chicks the incorporation of [U-(14)C]glucose and the activity of ;malic' enzyme did not increase unless the birds were fed. The response to feeding of [U-(14)C]glucose incorporation into fatty acids increased as the starved chicks grew older. 3. Citrate-cleavage enzyme activity increased slowly even when the newly hatched chicks were unfed. On feeding, citrate-cleavage enzyme activity increased at a much faster rate. 4. In normally fed 20-day-old chicks starvation decreased the incorporation of [U-(14)C]glucose into all three end products and depressed the activities of ;malic' enzyme and citrate-cleavage enzyme. Re-feeding increased all of these processes to normal or higher-than-normal levels. 5. In both newly hatched and 20-day-old chicks starvation increased the activity of isocitrate dehydrogenase and feeding or re-feeding decreased it. 6. Very little change in hexose monophosphate-shunt dehydrogenase activity was observed during the dietary manipulations. 7. The results indicate that increased substrate delivery to the liver is the principal stimulus to the increased rate of glucose metabolism observed in newly hatched chicks. The results also suggest that changes in the activities of ;malic' enzyme and citrate-cleavage enzyme are secondary to an increased flow of metabolites through the glucose-to-fatty acid pathway and that the dehydrogenases of the hexose monophosphate shunt play a minor role in NADPH production for fatty acid synthesis.     

Recovery from galactose-induced neurotoxicity in the chick by the administration of glucose

Abstract— Chicks fed a diet containing 40% (w/w) galactose demonstrated convulsive activity after 52–54 h. However, they recovered from both physical and biochemical symptoms temporarily, following the intraperitoneal injection of glucose. The previously decreased levels of ATP and elevated levels of AMP in the brains of chicks fed galactose returned to normal within 20 min following the glucose treatment. During the recovery phase, plasma glucose content rose and brain glucose returned to the normal range, whereas the levels of brain galactose and its metabolites, galactitol and galactose 1-phosphate, were unchanged. Moderate plasma hyperasmolality was induced in chicks fed the diet containing galactose and xylose or saline in the drinking water. Neurotoxicity was observed only in the group fed galactose, although brain glucose and glycogen were reduced in chicks fed xylose. In the brains of chicks fed xylose, xylitol was identified by gas-liquid chromatography and mass spectrometry, and the amount was approximately 10 per cent of the amount of xylose simultaneously found in the brain. These studies support the viewpoint that dietary galactose exerts its acute neurotoxicity in chicks primarily by inhibition of glucose transport across the blood-brain barrier.     

The effects of a pure protein diet on the amino-acid composition of Neomysis integer (Leach)

Neomysis integer (Leach) was fed lipid- and carbohydratc-free albumin or kaolin (starved) for up to eight days and the ability of the animal to maintain its total protein and free and protein amino-acid patterns was examined. Considerable effects on the body composition were seen although the amino-acid patterns of the diet and tissue protein were similar. Total protein was reduced to the same extent in both starved and albumin-fed animals, despite some utilization of the dietary protein. Conversely, the level of total free amino acid was reduced in starved animals but not in the protein-fed mysids. The amino-acid composition of the protein hydrolysates was altered after both starvation and feeding and the patterns produced indicated that protein synthesis, as well as catabolism had occurred in the albumin-fed animals. There were also changes in the composition of the free amino-acid pools of both starved and fed animals. In the starved samples taurine, aspartate, and arginine appeared to be conserved, while in the albumin-fed animals alanine, leucine, tyrosine and phenylalanine were substantially and consistently decreased, and arginine increased, in concentration. Although the results showed that the quality of the protein fraction was altered by the albumin diet, the amino-acid composition of the albumin had no direct effect on the resultant composition of either the protein hydrolysate or the free amino-acid pool in protein-fed animals.     

Fructose-induced hepatic gluconeogenesis: effect of L-carnitine

High fructose feeding (60 g/100 g diet) in rodents induces alterations in both glucose and lipid metabolism. The present study was aimed to evaluate whether intraperitoneal carnitine (CA), a transporter of fatty acyl-CoA into the mitochondria, could attenuate derangements in carbohydrate metabolizing enzymes and glucose overproduction in high fructose-diet fed rats. Male Wistar rats of body weight 150-160 g were divided into 4 groups of 6 rats each. Groups 1 and 4 animals received control diet while the groups 2 and 3 rats received high fructose-diet. Groups 3 and 4 animals were treated with CA (300 mg/Kg body weight/day, i.p.) for 30 days. At the end of the experimental period, levels of carnitine, glucose, insulin, lactate, pyruvate, glycerol, triglycerides and free fatty acids in plasma were determined. The activities of carbohydrate metabolizing enzymes and glycogen content in liver and muscle were assayed. Hepatocytes isolated from liver were studied for the gluconeogenic activity in the presence of substrates such as pyruvate, lactate, glycerol, fructose and alanine. Fructose-diet fed animals showed alterations in glucose metabolizing enzymes, increased circulating levels of gluconeogenic substrates and depletion of glycogen in liver and muscle. There was increased glucose output from hepatocytes of animals fed fructose-diet alone with all the gluconeogenic substrates. The abnormalities associated with fructose feeding such as increased gluconeogenesis, reduced glycogen content and other parameters were brought back to near normal levels by CA. Hepatocytes from these animals showed significant inhibition of glucose production from pyruvate (74.3%), lactate (65.4%), glycerol (69.6%), fructose (56.2%) and alanine (63.6%) as compared to CA untreated fructose-fed animals. The benefits observed could be attributed to the effect of CA on fatty acyl-CoA transport.     

Carbohydrate metabolism in starved fifth instar larvae of Manduca sexta

The influence of starvation on carbohydrate metabolism in fifth instar larvae of Manduca sexta was studied. The percentage of active fat body glycogen phosphorylase increased from 10% to approximately 50% within 3 h of starvation; afterward the enzyme was slowly inactivated. The increase of phosphorylase activity might have been caused by a peptide(s) from the CC. The amount of fat body glycogen in starved animals decreased over 24 h by approximately 20 mg. The released glucose molecules seem to be converted mainly to trehalose because the hemolymph trehalose concentration in starved animals was always slightly higher than in the fed controls, and the glucose concentration decreased even when phosphorylase was activated. The chitosan content in starved larvae increased during the first 9 h of treatment to the same extent as in fed controls. It is suggested that fat body glycogen phosphorylase was activated during starvation to provide substrates for chitin synthesis and energy metabolism.     

Role of the rat liver in the disposal of a glucose gavage

An oral gavage of either 3, 1 or 0.1 mmoles of glucose was given to rats under standard feeding conditions or food deprived for 24 hr. The blood flow of the portal and suprahepatic veins as well as the hepatic balances for glucose, lactate, alanine and pyruvate were estimated.In fed rats, after the administration of an oral 3 mmoles load, the liver actually released 310 µmoles of glucose and 90 of lactate, amounts that could be accounted for by the uptake of alanine (148 µmoles) and small loss of glycogen (275 µmoles of glycosyl residues). In starved rats, however, the liver took a very high proportion (c. 71%) of the glucose absorbed, both as glucose (780 µmoles), lactate and pyruvate (892 µmoles) or alanine (134 µmoles). The synthesis of glycogen was considerably limited, accounting for only 205 µmoles, and leaving practically one mmol of glucose equivalent energy available for liver function and the synthesis of other compounds. Practically all glycogen was synthesized directly from glucose, since the synthesis from 3 C carriers was less than a 5%. Smaller gavages (1 or 0.1 mmoles) resulted in a much lower liver uptake activity.The strikingly different activity of the liver with respect to the available glucose and 3 C fragments could not be explained alone by the circulating levels of these compounds, suggesting a very deep influence of the intestine in hepatic function. The liver plays a very passive role in fed animals, with a very small involvement in the disposal of a glucose load, whereas it takes on an important role when the overall availability of energy is diminished.     

Dietary whey protein modulates liver glycogen level and glycoregulatory enzyme activities in exercise-trained rats

This study compared the effects of dietary whey protein with dietary casein or soy protein on glycogen storage and glycoregulatory enzyme activities in the liver of sedentary and exercise-trained rats. Male Sprague-Dawley rats (ca. 130 g) were divided into one sedentary and three exercise-trained groups, with eight animals in each group. Casein was provided as the source of dietary protein in the sedentary group while the exercise-trained groups were fed casein, whey, or soy protein. Rats in the exercise-trained groups ran for 30 mins/day, 4 days/week on a motor-driven treadmill. In the exercise-trained rats, animals fed whey protein had higher liver glycogen content than animals in the other two diet groups. Glucokinase activity was significantly higher in rats fed whey protein compared to that in rats fed soy protein, while glucose 6-phosphatase activity was significantly decreased in animals on the whey protein diet compared with those the other two diets. Although 6-phospho-fructokinase activity was significantly lower in the whey protein group than in the soy protein group, we found that fructose 1,6-bisphosphatase activity was significantly higher in the whey group compared with either the casein or soy groups. Pyruvate kinase activity in rats fed the casein diet was significantly higher than in rats fed either the whey or soy protein diets. In addition, hepatic alanine aminotransferase activity and serum alanine level were also increased in the whey protein group compared with the casein or soy protein groups. Taken together, these results demonstrate that the whey protein diet in exercise-trained rats results in significantly higher levels of liver glycogen, because of the combined effects of regulation of rate limiting glycolytic and gluconeogenic enzyme activities and activation of glycogenesis from alanine via alanine amino-transferase.     

The actions of dichloroacetic acid on blood glucose, liver glycogen and fatty acid synthesis in obese-hyperglycaemic (ob/ob) and lean mice

Obese-hyperglycaemic mice and lean mice were injected with dichloroacetate to determine the significance of gluconeogenesis in maintaining the hyperglycaemia of obese mice and to investigate the effects of a fall in blood glucose on fatty acid synthesis. One hour after the second of two, hourly, injections of dichloroacetate the blood glucose concentrations in fed and starved lean mice were decreased, whereas in obese mice they were sharply increased. In obese and lean mice, both fed and starved, dichloroacetate decreased plasma lactate but insulin was unchanged. The quantity of liver glycogen was decreased in all dichloroacetate treated mice, with the largest falls in fed and starved obese mice, which had much larger glycogen stores than lean mice. Dichloroacetate treatment decreased the concentration of plasma non-esterified fatty acids in fed and starved obese mice and fed lean mice but not in starved lean mice. Fatty acid synthesis in white (inguinal, subcutaneous) adipose tissue was stimulated by dichloroacetate in fed obese mice and inhibited in fed lean mice. Fatty acid synthesis in brown adipose tissue (scapular) was faster than in white adipose tissue and was less affected by dichloroacetate although the changes were in the same direction as in white adipose tissue. We attribute the increased hyperglycaemia of obese mice treated with dichloroacetate to increased glycogenolysis coupled with a failure to secrete additional insulin in response to the raised blood glucose. This high blood glucose concentration in dichloroacetate treated obese mice may in turn explain the increased fatty acid synthesis in their white adipose tissue.     

Effects of sugar feeding on carbohydrate and lipid metabolism in a parasitoid wasp

Lifetime patterns of carbohydrate and lipid metabolism were compared in starved and sucrose‐fed adults of the parasitoid Macrocentrus grandii (Goidanich) (Hymenoptera: Braconidae). As expected, sucrose‐fed individuals lived longer than did starved individuals. Macrocentrus grandii males and females eclosed with levels of simple storage sugars (presumably primarily trehalose) and glycogen that were below maximum levels recorded from sucrose‐fed parasitoids. Both of these nutrients dropped to very low levels in starved individuals within 4 days post‐emergence and were maintained at high levels in sucrose‐fed individuals throughout their lives. Lipid reserves at emergence represented the highest lipid levels for both sexes in the two diet treatments, with levels declining over the lifetimes of males and females from both diet treatments. Our results therefore suggest that dietary sucrose is used to synthesize trehalose and glycogen, but not lipids in M. grandii. Also, in contrast to the patterns observed for the simple sugars and glycogen, lipid levels in starved individuals did not drop below levels observed in sugar‐fed individuals. The average number of mature eggs carried by females at emergence was 33 and increased to approximately 85 in sucrose‐fed and 130 in starved females by the age of 5 d in the absence of hosts. The egg maturation rate was therefore higher in starved than in sugar‐fed females. Potential explanations for this unexpected result are discussed.     

Effect of starvation and protein-feeding on blood amino acid compartmentation of domestic fowl hatchlings

The amino acid concentrations in plasma and blood cells of 5-day old domestic fowl hatchlings that received either standard feeding, protein-feeding or were starved have been determined. The effects of 5-day starvation or protein feeding did not alter significantly the combined amino acid concentration of blood plasma, but decreased blood cell levels. The patterns of individual amino acid changes observed in starvation or protein-feeding were similar in both groups when compared with those of controls. However, starvation-induced effects were actually more marked than those observed in protein-fed animals. The patterns of change with starvation of individual amino acids in the hatchling blood compartments were very different from those observed in mammals subjected to short or medium-term starvation. The mechanisms controlling circulating amino acid concentrations act in both situations studied to maintain the plasma amino acid concentrations despite marked changes in the availability of 2-amino nitrogen energy to the animal; changes in blood amino acid compartmentation buffering plasma amino acid availability.     

Daily changes in parameters of energy metabolism in liver, white muscle, and gills of rainbow trout: dependence on feeding

We assessed the daily patterns of parameters involved in energy metabolism in liver, white muscle, and gills of rainbow trout. Where daily rhythms were found, we analyzed the potential influence of feeding. Immature rainbow trout were randomly distributed in 3 groups: fish fed for 7 days, fish fasted for 7 days, and fish fasted for 7 days and refed for 4 days. On sampling day, fish of fed and refed groups were fed at 11.00 h, and all fish were sampled from each treatment group using the following time schedule: 14.00, 18.00, 21.00, 00.00, 04.00, 07.00, 10.00 and 14.00 h. The results obtained from metabolic parameters can be grouped into four different categories, such as i) those displaying no daily changes in any group assessed in liver (acetoacetate and lactate levels), white muscle (protein levels, and low Km (glucose) hexokinase (HK) and HK-IV activities) and gills (protein levels), ii) those displaying no 24 h changes in fed fish but in refed or fasted fish in liver (glucose, glycogen, amino acid and protein levels, and HK-IV activity), white muscle (glycogen and amino acid levels) and gills (glucose levels), iii) those displaying 24 h changes that were apparently dependent on feeding since they disappear in fasted fish in liver (Low Km (glucose) HK, lactate dehydrogenase (LDH-O), glucose 6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBPase) , alpha-glycerophosphate dehydrogenase (G3PDH), glutamate dehydrogenase (GDH) and aspartate aminotransferase (Asp-AT) activities), white muscle (glucose levels, and pyruvate kinase (PK), LDH-O, G3PDH and Asp-AT activities) and gills (glycogen and lactate levels, and Low Km (glucose) HK, HK-IV, LDH-O and Asp-AT activities), and iv) those parameters displaying 24 h changes apparently not dependent on feeding in liver (lactate levels and PK activity) and gills (amino acid levels, and PK and GDH activities). In general, most 24 h changes observed were dependent on feeding and can be also related to daily changes in activity.     

Glucose metabolism in perfused skeletal muscle. Effects of starvation, diabetes, fatty acids, acetoacetate, insulin and exercise on glucose uptake and disposition.

1. The regulation of glucose uptake and disposition in skeletal muscle was studied in the isolated perfused rat hindquarter. 2. Insulin and exercise, induced by sciatic-nerve stimulation, enhanced glucose uptake about tenfold in fed and starved rats, but were without effect in rats with diabetic ketoacidosis. 3. At rest, the oxidation of lactate (0.44 mumol/min per 30 g muscle in fed rats) was decreased by 75% in both starved and diabetic rats, whereas the release of alanine and lactate (0.41 and 1.35 mumol/min per 30 g respectively in the fed state) was increased. Glycolysis, defined as the sum of lactate+alanine release and lactate oxidation, was not decreased in either starvation or diabetes. 4. In all groups, exercise tripled O2 consumption (from approximately 8 to approximately 25 mumol/min per 30 g of muscle) and increased the release and oxidation of lactate five- to ten-fold. The differences in lactate release between fed, starved and diabetic rats observed at rest were no longer apparent; however, lactate oxidation was still several times greater in the fed group. 5. Perfusion of the hindquarter of a fed rat with palmitate, octanoate or acetoacetate did not alter glucose uptake or lactate release in either resting or exercising muslce; however, lactate oxidation was significantly inhibited by acetoacetate, which also increased the intracellular concentration of acetyl-CoA. 6. The data suggest that neither that neither glycolysis nor the capacity for glucose transport are inhbitied in the perfused hindquarter during starvation or perfusion with fatty acids or ketone bodies. On the other hand, lactate oxidation is inhibited, suggesting diminished activity of pyruvate dehydrogenase. 7. Differences in the regulation of glucose metabolism in heart and skeletal muscle and the role of the glucose/fatty acid cycle in each tissue are discussed.