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

A 24-h starvation markedly diminished the stimulant action of 8 mM glucose on insulin secretion from isolated perifused rat islets of Langerhans. The response to a supramaximal glucose stimulus (27.5 mM) remained normal, but prolonged fasting (48 or more) also reduced its efficacy. Refeeding of 24-h fasted animals resulted in complete restoration of glucose sensitivity within 24 h. The responses to glyceraldehyde (2 mM) and alpha-ketoisocaproate (8 mM) at concentrations which elicit approximately half-maximal stimulation were unaltered by a 24-h fast, while that to a half-maximally effective dose of mannose (15 mM) was decreased. Theophylline (5 mM) could not normalize the reduced secretory response to glucose seen in this state. The islets' ability to metabolize glucose, using various in vitro pretreatment protocols and different incubation times, was not affected by a 24-h fast. Mannose and glyceraldehyde metabolism were also unaltered. Prolonged fasting (48 h) reduced glucose metabolism by 25% at both 8 and 27.5 mM. The acute adaptive changes in islet sensitivity to moderate glucose and mannose concentrations during short term fasting (24 h) cannot be explained by an altered usage of the added hexoses.
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PMID:Starvation diabetes in the rat: onset, recovery, and specificity of reduced responsiveness of pancreatic beta-cells. 37 69

The effect of L-carnitine (0.5-2.0 mM) on the rates of alpha-decarboxylation of 1-14C-labeled branched-chain amino acids by gastrocnemius muscle and liver homogenates of fed rats was investigated. Carnitine increased the rate of alpha-decarboxylation of leucine (125%) and valine (28%) by muscle, but it was without effect on the oxidation of these amino acids by liver. Carnitine increased the rate of alpha-decarboxylation of alpha-ketoisocaproate by both tissues. This effect was more pronounced in muscle (130% increase) than in liver (41% increase). The activity of carnitine acyltransferase, with isovaleryl-CoA as a substrate, was 18 times higher in muscle mitochondria than in liver mitochondria. Both starvation and diabetes increased the rate of alpha-decarboxylation of leucine by muscle without having a remarkable effect on the concentration of carnitine or the activity of carnitine acyltransferase. We conclude that: a) carnitine stimulates decarboxylation of branched-chain amino acids by increasing the conversion of their ketoanalogues into carnitine esters, b) a greater carnitine acyltransferase activity in muscle than in liver may be responsible for the greater carnitine effect in muscle, c) carnitine does not appear responsible for the enhancement of leucine oxidation by muscle of starved and diabetic rats.
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PMID:Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle. 64 1

The rate of protein synthesis in skeletal muscle was determined in the post-absorptive state and after 3 days of starvation in healthy volunteers. The flooding dose technique employing intravenous injection of (1-13C)leucine (0.05 g kg-1) was used and incorporation of isotope into muscle protein was measured by taking percutaneous biopsies at 0 and 90 min. Blood samples were taken during the incorporation period for assessment of the enrichment of the free amino acid precursor of protein synthesis. The median (25,75 quartiles) rate of muscle protein synthesis after an overnight fast was 2.03 (2.00,2.23) % days-1 when the precursor enrichment was obtained by measurement of the plasma alpha-ketoisocaproate, taken to be representative of muscle free leucine. Repeat measurements in the same subjects after 3 days of total starvation showed a decrease to 1.82 (1.57,2.05) % days-1. Rates calculated on the basis of the plasma leucine as precursor were 5% lower at both times. An interindividual variation in response to starvation was observed, but the median decrease of 13% in the rate of protein synthesis was statistically significant (P less than 0.01).
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PMID:Short-term starvation decreases skeletal muscle protein synthesis rate in man. 160 11

By use of a primed continuous infusion of [1-14C]leucine, we investigated parameters of leucine metabolism in plasma, expired air, and tissues of fed and 48-h starved rats. The ratios of muscle to plasma specific activity of alpha-ketoisocaproate (KIC) in fed and starved rats were not significantly different from 1. The ratio of muscle to plasma specific activity of leucine was also not significantly different from 1 in fed rats, but was significantly lower than 1 in starved rats. The rate of leucine oxidation was 28-34% higher when calculation was based on plasma KIC rather than leucine specific activity. However, starvation significantly increased the rate of leucine oxidation with either specific activity. The rates of leucine incorporation into whole-body protein, calculated as the difference between plasma leucine turnover and oxidation, were unaffected by starvation, but the incorporations into total protein measured directly were significantly decreased in liver and muscle. We conclude that leucine or KIC specific activity in muscle is better predicted by plasma KIC than leucine specific activity, and the difference between rates of plasma leucine turnover and oxidation does not appear to be a valid measurement of leucine incorporation into whole-body protein.
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PMID:Relation between plasma and tissue parameters of leucine metabolism in fed and starved rats. 308 15

A number of alpha-keto acid analogs of amino acids have been found to penetrate the blood-brain barrier (BBB). Pyruvate, alpha-ketobutyrate, alpha-ketoisocaproate, and alpha-keto-gamma-methiolbutyrate all cross the BBB by a carrier-mediated process and by simple diffusion. Under normal physiological conditions, diffusion accounts for roughly 15% or less of total transport. Aromatic alpha-keto acids, phenylpyruvate, and p-hydroxyphenylpyruvate do not penetrate the BBB, nor do they inhibit the transport of other alpha-keto acids. Evidence based primarily on inhibition studies indicates that the carrier-mediated transport of alpha-keto acids occurs via the same carrier demonstrated previously for propionate, acetoacetate, and beta-hydroxybutyrate transport, commonly referred to as the monocarboxylate carrier. As a group, the alpha-keto acid analogs of the amino acids have the highest affinity for the carrier, followed by propionate and beta-hydroxybutyrate. Starvation for 4 days induces transport of alpha-keto acids, but transport is suppressed in rats fed commercial laboratory rations and subjected to portacaval shunts. The mitochondrial pyruvate translocator inhibitor alpha-cyanocinnamate has no effect on the BBB transport of alpha-keto acids.
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PMID:Blood-brain barrier transport of the alpha-keto acid analogs of amino acids. 351 90

Whole-body leucine kinetics and rectus muscle synthetic rates were evaluated in postabsorptive rats fed semipurified diets that varied in the casein content. Rats were allowed to consume ad libitum a 2% casein diet or were pair-fed or ad libitum-fed 6, 20, or 40% casein diets for 14 days. After overnight starvation, rates of whole-body leucine kinetics and rectus muscle synthetic rates were determined with a 2-h constant intravenous infusion of L-[1-14C]leucine. The postabsorptive response to inadequate protein intakes included a significant reduction in the release of leucine from whole-body protein degradation as well as subsequent reutilization for protein synthesis. In contrast, dietary protein intake at levels greater than required for maximal growth were not associated with any increases in leucine incorporation into whole-body protein or muscle fractional synthetic rates. Rates of whole-body leucine oxidation based on plasma leucine specific radioactivities underestimated total oxidation by 22-27%, and this was relatively constant as the protein component of the diet was varied. In addition, the muscle acid-soluble leucine specific radioactivity was similar to the plasma alpha-ketoisocaproate enrichment, regardless of dietary protein intake.
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PMID:Whole-body leucine and muscle protein kinetics in rats fed varying protein intakes. 642 16

We measured the effects of seven consecutive daily infusions of alpha-ketoisocaproate (the alpha-keto analogue of leucine) or leucine itself on urinary urea and total nitrogen excretion during fasting. Two study protocols were undertaken. In protocol I, subjects underwent three separate 14-d fasts: one during which 34 mmol/d of leucine were infused on days 1--7; a second during which 34 mmol/d of alpha-ketoisocaproate were infused on days 1--7; and a third control fast during which no infusions were given. Infusions of alpha-ketoisocaproate significantly reduced daily urine urea nitrogen excretion compared with both the control fasts and the fasts in which leucine was infused (P less than 0.001). This nitrogen-sparing effect of alpha-ketoisocaproate persisted during days 8--14 even though no further infusions were given. Daily urinary urea nitrogen excretion during fasts when leucine was administered did not differ from values observed during control fasts. In protocol II, subjects were starved on two occasions for 14 d. During one fast, infusions of 11 mmol/d of alpha-ketoisocaproate were given on days 1--7; during the control fast, no infusions were given. Daily urine urea nitrogen excretion was lower (P less than 0.001) on days 1--7 and also on days 8--14 of the fast during which alpha-ketoisocaproate was given. The nitrogen-sparing effect of alpha-ketoisocaproate could not be related to changes in circulating levels of amino acids, ketone bodies, or insulin in either protocol. We conclude that alpha-ketoisocaproate infusions decrease the nitrogen wasting of starvation, whereas leucine, studied under identical conditions, does not.
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PMID:Nitrogen sparing induced by leucine compared with that induced by its keto analogue, alpha-ketoisocaproate, in fasting obese man. 746 28

The hypothesis that a defect in glucose sensing by islets of fa/fa Zucker rats contributes to hyperinsulinemia in these animals was tested. Islets from lean and fa/fa rats were isolated by collagenase digestion and step-density gradient purification and then cultured overnight in Dulbecco's modified Eagle's medium containing 12.5 mM glucose. Obese rat islets were more sensitive to hypoglycemic glucose levels with half-maximal effective concentration (EC50) of 5.6 mM compared with an EC50 of 8.2 mM for lean rat islets. In contrast, responsiveness of both phenotypes to alpha-ketoisocaproate and quinine was similar. Mannoheptulose did not inhibit insulin secretion from fa/fa islets, although inhibitors of later events in the stimulus-secretion coupling pathway were normally inhibited by iodoacetate and diazoxide. Finally, starvation in vivo and culture of islets in low glucose concentrations (5 mM) in vitro both decreased glucose-stimulated insulin secretion from lean but not fa/fa rat islets. We conclude that fa/fa rat islets have an exaggerated insulin response to hypoglycemic stimuli, possibly as a result of a defect in B-cell glucokinase function.
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PMID:Evidence for defective glucose sensing by islets of fa/fa obese Zucker rats. 851 32

The effects of acute food deprivation and subsequent refeeding with isonitrogenous oral liquid diets supplemented with arginine (ARG), ARG alpha-ketoglutarate (AKG), or ARG alpha-ketoisocaproate (AKIC) were examined in a Sprague-Dawley rat trauma model (bilateral femur fracture). Both control and trauma rats were starved for 2 days and then pair-fed for 4 days with one of four liquid isonitrogenous diets: diet 1 was a basal casein-based diet, and diets 2, 3, and 4 were the basal diet in which 10% of the nitrogen was replaced by ARG, AKG, or AKIC nitrogen. Two days of starvation resulted in a 13% loss of body weight and also a 27% decrease in the excretion of orotic acid (OA) in control and trauma rats. Although the ARG content of diets 2, 3, and 4 was the same, ARG- and AKIC-supplemented rats excreted significantly (P < .05) more OA than AKG-fed rats. The low level of OA excretion in AKG-fed rats indicates greater use of ARG for metabolic purposes, including efficient urea cycle operation. The metabolic adaptation and nutritional efficacy, i.e., Increased nitrogen retention, larger weight gain, and altered amino acid (AA) metabolism, of AKIC rats seem to be better than in ARG- or AKG-fed rats.
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PMID:Nutritional and metabolic effects and significance of mild orotic aciduria during dietary supplementation with arginine or its organic salts after trauma injury in rats. 922 32

Rats were fasted for 48 h, but infused with either NaCl or the sodium salt of monoethyl succinic acid (EMS), both delivered at a rate of 80 mumol/g body weight per day. The infusion of EMS, as compared to NaCl, failed to affect paraovarian adipose tissue or liver weight, liver or muscle glycogen, and insulinemia. It accentuated the starvation-induced fall in body weight, and decreased both liver and muscle protein content. Nevertheless, the succinate ester increased plasma D-glucose concentration, delayed the rise in ketonemia, maintained a higher glucokinase/hexokinase activity ratio in liver and pancreatic islets, and allowed for a more efficient stimulation of insulin release by D-glucose or 2-ketoisocaproate in isolated pancreatic islets. These findings indicate that monoethyl succinate displays a significant nutritional value when infused in starved rats.
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PMID:Nutritional value of succinic acid monoethyl ester in starvation. 926 86


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