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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite significant increases in circulating concentrations of lipid fuels (triacylglycerol, non-esterified fatty acids (NEFA) and ketone bodies) in late-pregnant rats sampled in the fed (absorptive) state, cardiac and skeletal muscle active pyruvate dehydrogenase (PDHa) activities remained comparable with those observed in fed, age-matched virgin controls. Cardiac PDHa activity was suppressed in response to acute (6 h) starvation in late-pregnant (as well as virgin) rats: this inactivation was opposed by inhibition of mitochondrial long-chain FA oxidation. Starvation (6 h) also led to PDH inactivation in skeletal muscles of late-pregnant, but not virgin, rats. Starvation for 24 h led to further suppression of cardiac PDHa activity and was associated with significant increases in PDH kinase activities in both virgin and late-pregnant rats. Late pregnancy did not itself influence cardiac PDH kinase activity.
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PMID:Control of muscle pyruvate oxidation during late pregnancy. 847 40

Glucose utilization indices (GUI) were measured in vivo in conjunction with active pyruvate dehydrogenase complex (PDH(a) and glycogen synthase (GS) activities in fast-twitch skeletal muscles [extensor digitorum longus (EDL), tibialis anterior and gastrocnemius] of late-pregnant rats and age-matched virgin control rats in the fed state, after 24 h starvation and at 2 h after re-feeding with standard laboratory chow ad libitum after 24 h starvation. As demonstrated previously [Holness and Sugden (1990) Biochem. J 277, 429-433], GUI values of fast-twitch skeletal muscles of virgin rats were low in the fed ad libitum and the 24 h-starved states, but dramatically increased after subsequent chow re-feeding. GUI values of fast-twitch skeletal muscles of late-pregnant rats were also low in the fed and starved states and were increased by re-feeding, but the increase in GUI values elicited by re-feeding was greatly attenuated. PDHa activities in EDL, tibialis anterior and gastrocnemius in the fed state were unaffected by late pregnancy, and skeletal-muscle PDHa activities were decreased after 24 h of starvation in both groups. Whereas re-feeding of virgin rats with standard diet for 2 h restored PDHa activities in fast-twitch skeletal muscles to values for rats continuously fed ad libitum, PDHa activities in fast-twitch skeletal muscles of late-pregnant rats, although increased in response to re-feeding, remained considerably less than the corresponding fed ad libitum values after 2 h of re-feeding. In contrast, neither skeletal-muscle GS re-activation nor rates of skeletal-muscle glycogen deposition after re-feeding were markedly affected by late pregnancy. The results are discussed in relation to the specific targeting of individual pathways of glucose disposal in fast-twitch skeletal muscles during re-feeding in late pregnancy.
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PMID:Changes in rates of glucose utilization and regulation of glucose disposal by fast-twitch skeletal muscles in late pregnancy. 850 77

Gluconeogenesis from isotopically substituted (3-13C)alanine (Ala) was demonstrated in the last larval instar of an insect, Manduca sexta, when maintained on low carbohydrate diets. 13C was incorporated into all carbons of the blood sugar trehalose (Tre), but enrichments of C1 and C6, and C2 and C5 were greatest. Relative to the amount of [3-13C]Ala metabolized, larvae maintained on a low carbohydrate diet supplemented with casein displayed the greatest enrichment of Tre. Very little de novo synthesis of Tre was observed in larvae maintained on a complete-balanced diet containing calorically equivalent amounts of sucrose and casein. Starvation failed to induce gluconeogenesis and 13C was not incorporated into Tre in starved insects. Activity of the TCA cycle contributed approximately 10% of the 13C incorporated into Tre in larvae on low carbohydrate diets, while the TCA cycle contribution in larvae on the complete diet approached 70%. The pattern of 13C enrichment of glucose in larvae on the low carbohydrate diets indicated that cytoplasmic carboxylation, possibly due to 'malic enzyme'-like activity, contributed significantly to the synthesis of Tre. The pentose phosphate pathway was evidenced in insects on all diets. Glucose labelling ratios indicated a pentose cycling flux of 10 to 20% in insects on the low carbohydrate diets and 50% in larvae on the complete diet. Glutamine together with lesser amounts of glutamate and glutathione were also products of the labelled Ala. The distribution of label in these products under different dietary conditions demonstrated shifts in the relative contribution of pyruvate carboxylase and pyruvate dehydrogenase activities for providing substrate to the TCA cycle. In the expected fashion starved insects and insects on the low carbohydrate diets incorporated a greater proportion of 13C into the TCA cycle via carboxylation while incorporation by the two pathways was similar in insects on the complete diet. The significance of these findings with regard to the regulation of gluconeogenesis in M. sexta and comparison of the present results with those obtained from studies of hepatic gluconeogenesis are discussed.
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PMID:Gluconeogenesis and effect of nutritional status on TCA cycle activity in the insect Manduca sexta. 854 15

The provision of a high-fat diet (47% of energy as fat) for 28 days led to a significant increase in hepatic pyruvate dehydrogenase kinase activity, together with significant suppression of hepatic pyruvate dehydrogenase (active form). An enhanced hepatic pyruvate dehydrogenase kinase activity continued to be observed at 6 h after the withdrawal of the high-fat diet. Significant suppression of hepatic pyruvate dehydrogenase kinase activity was observed in post-absorptive, high-fat-fed rats after a 2.5 h euglycaemic-hyperinsulinaemic clamp, such that differences in pyruvate dehydrogenase kinase activities between control and high-fat-fed rats were no longer evident. Starvation for 24 h in rats previously maintained on standard diet also evoked a substantial increase in hepatic pyruvate dehydrogenase kinase activity. This latter response was only partially reversed by 2.5 h of euglycaemic hyperinsulinaemia. Suppression of pyruvate dehydrogenase kinase activity by 2.5 h euglycaemic hyperinsulinaemia in high-fat-fed rats was associated with a substantial increase in hepatic pyruvate dehydrogenase activity (active form) whereas no significant increase in hepatic pyruvate dehydrogenase activity (active form) was observed after 2.5 h euglycaemic hyperinsulinaemia in 24 h-starved rats. The results are consistent with the proposition that hepatic pyruvate dehydrogenase kinase responds directly to an increase in lipid oxidation which is facilitated by insulin deficiency or an impaired action of insulin.
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PMID:Regulation of hepatic pyruvate dehydrogenase kinase by insulin and dietary manipulation in vivo. Studies with the euglycaemic-hyperinsulinaemic clamp. 867 48

The transplacental supply of nutrients is interrupted at birth, which diverts maternal metabolism to lactation. After birth, energy homeostasis is rapidly regained through milk nutrients which supply the newborn with the fatty acids and ketone bodies required for neonatal development. However, immediately after birth and before the onset of suckling there is a time lapse in which the newborn undergoes a unique kind of starvation. During this period glucose is scarce and ketone bodies are not available owing to the delay in ketogenesis. Under these circumstances, the newborn is supplied with another metabolic fuel, lactate, which is utilized as a source of energy and carbon skeletons. Neonatal rat lung, heart, liver and brain utilize lactate for energy production and lipogenesis. Lactate is also utilized by the brain of human babies with type I glycogenosis. Both rat neurons and astrocytes in primary culture actively use lactate as an oxidizable substrate and as a precursor of phospholipids and sterols. Lactate oxidation is enhanced by dichloroacetate, an inhibitor of the pyruvate dehydrogenase kinase in neurons but not in astrocytes, suggesting that the pyruvate dehydrogenase is regulated differently in each type of cell. Despite the low activity of this enzyme in newborn brain, pyruvate decarboxylation is the main fate of glucose in both neurons and astrocytes. The occurrence of a yeast-like pyruvate decarboxylase activity in neonatal brain may explain these results.
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PMID:Metabolic fuel utilization and pyruvate oxidation during the postnatal period. 888 67

Effects of aging on the activities of heart pyruvate dehydrogenase complex and pyruvate dehydrogenase kinase were examined using 7, 35 and 60 wk old rats. Aging did not affect the total activity of pyruvate dehydrogenase complex but decreased the activity state (percentage of active form) of the complex in rats under the fed condition (52%, 36% and 26% for 7, 35 and 60 wk old rats, respectively). This decrease in the complex activity with aging was suggested to be associated with an age-related decrease in the blood glucose disposal. Starvation for 24 h decreased the activity state to less than 3% in all of the age groups. The activity of pyruvate dehydrogenase kinase associated with the complex was not related to the alteration in the activity state of the complex; the kinase activity was slightly lower in 60 wk old rats than in the younger rats under the fed condition and activation of the kinase by starvation was greater in the younger rats. The mechanism for the decrease in activity of pyruvate dehydrogenase complex was discussed on the basis of glucose and fatty acid utilization of heart muscle cells.
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PMID:Effects of aging on the activities of pyruvate dehydrogenase complex and its kinase in rat heart. 919 86

The administration of a low-carbohydrate/high-saturated-fat (LC/HF) diet for 28 days or starvation for 48 h both increased pyruvate dehydrogenase kinase (PDHK) activity in extracts of rat hepatic mitochondria, by approx. 2.1-fold and 3.5-fold respectively. ELISAs of extracts of hepatic mitochondria, conducted over a range of pyruvate dehydrogenase (PDH) activities, revealed that mitochondrial immunoreactive PDHKII (the major PDHK isoform in rat liver) was significantly increased by approx. 1.4-fold after 28 days of LC/HF feeding and by approx. 2-fold after 48 h of starvation. The effect of LC/HF feeding to increase hepatic PDHK activity was retained through hepatocyte preparation, but was decreased on 21 h culture with insulin (100 micro-i.u./ml). A sustained (24 h) 2-4-fold elevation in plasma insulin concentration in vivo (achieved by insulin infusion via an osmotic pump) suppressed the effect of LC/HF feeding so that hepatic PDHK activities did not differ significantly from those of (insulin-infused) control rats. The increase in hepatic PDHK activity evoked by 28 days of LC/HF feeding was prevented and reversed (within 24 h) by the replacement of 7% of the dietary lipid with long-chain omega-3 fatty acids. Analysis of hepatic membrane lipid revealed a 1.9-fold increase in the ratio of total polyunsaturated omega-3 fatty acids to total mono-unsaturated fatty acids. The results indicate that the increased hepatic PDHK activities observed in livers of LC/HF-fed or 48 h-starved rats are associated with long-term actions to increase hepatic PDHKII concentrations. The long-term regulation of hepatic PDHK by LC/HF feeding might be achieved through an impaired action of insulin to suppress PDHK activity. In addition, the fatty acid composition of the diet, rather than the fat content, is a key influence.
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PMID:Studies of the long-term regulation of hepatic pyruvate dehydrogenase kinase. 940 79

This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart. Immunoblot analysis revealed a remarkable increase in the amount of PDK4 in the hearts of rats that had been starved or rendered diabetic with streptozotocin. Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats. Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls. In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes. The observed shift in the relative abundance of PDK isoenzymes probably explains previous studies of the effects of starvation and diabetes on heart PDK activity. The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.
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PMID:Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart. 940 94

To better define the modifications of liver gluconeogenesis and citric acid cycle, or Krebs' cycle, activity induced by insulin deficiency and the effects of metformin on these abnormalities, we infused livers isolated from postabsorptive or starved normal and streptozotocin-induced diabetic rats with pyruvate and lactate (labeled with [3-13C]lactate) with or without the simultaneous infusion of metformin. Lactate and pyruvate uptake and glucose production were calculated. The 13C-labeling pattern of liver glutamate was used to calculate, according to Magnusson's model, the relative fluxes through Krebs' cycle and gluconeogenesis. These relative fluxes were converted into absolute values using substrate balances. In normal rats, starvation increased gluconeogenesis, the flux through pyruvate carboxylase-phosphoenolpyruvate carboxykinase (PC-PEPCK), and the ratio of PC to pyruvate dehydrogenase (PDH) flux (P < 0.05); metformin induced only a moderate decrease in the PC:PDH ratio. Livers from postabsorptive diabetic rats had increased lactate and pyruvate uptakes (P < 0.05); their metabolic fluxes resembled those of starved control livers, with increased gluconeogenesis and flux through PC-PEPCK. Starvation induced no further modifications in the diabetic group. Metformin decreased glucose output from the liver of starved diabetic rats (P < 0.05). The flux through PC-PEPCK and also pyruvate kinase were decreased (P < 0.05) by metformin in both groups of diabetic rats. In conclusion, insulin deficiency increased in this model of diabetes gluconeogenesis through enhanced uptake of substrate and increased flux through PC-PEPCK; metformin decreased glucose production by reducing the flux through PC-PEPCK.
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PMID:Modifications of citric acid cycle activity and gluconeogenesis in streptozotocin-induced diabetes and effects of metformin. 1034 12

The yeast LPD1 gene encoding lipoamide dehydrogenase is subject to the general control of amino acid biosynthesis mediated by the GCN4 transcription factor. This is striking in that it demonstrates that GCN4-mediated regulation extends much farther upstream than simply to the direct pathways for amino acid and purine biosynthesis. In yeast, lipoamide dehydrogenase functions in at least three multienzyme complexes: pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase (which function in the entry of pyruvate into, and metabolism via, the citric acid cycle) and glycine decarboxylase. When wild-type cells were shifted from growth on amino acid-rich to amino acid-deficient medium, the expression of lipoamide dehydrogenase was induced approx. 2-fold. In a similar experiment no such induction was observed in isogenic gcn4 mutant cells. Northern analysis indicated that amino acid starvation affected levels of the LPD1 transcript. In the upstream region of LPD1 are three matches to the consensus for control mediated by GCN4. Directed mutagenesis of each site, and of all combinations of sites, suggests that only one site might be important for the general control response under the conditions tested. Gel-retardation analysis with GCN4 protein synthesized in vitro has indicated that GCN4 can bind in vitro to at least two of the consensus motifs.
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PMID:Transcription factor GCN4 for control of amino acid biosynthesis also regulates the expression of the gene for lipoamide dehydrogenase. 1035 73


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