Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-Carnitine plays a crucial role in the perinatal transition from carbohydrate to lipid-derived energy. To examine the potential contribution of assimilated dietary carnitine to the elevated hepatic concentrations in newborns, we measured carnitine concentrations in sow milk, jejunum, and liver, and in vitro jejunal carnitine transport in piglets aged 1-36 d. Hepatic and sow milk total carnitine concentrations peaked soon after birth and declined with age (p = 0.035 and 0.026, respectively). Although jejunal total carnitine concentrations remained stable, jejunal carnitine flux was higher at 2 d of age than in older piglets. To examine the possible signals that regulate hepatic carnitine, portal enteroinsular hormones were measured by RIA. Portal glucagon (p = 0.0006), insulin (p = 0.0001), and glucagon:insulin ratio (p = 0.037) were related to age. Portal glucagon was highest in newborns and during weaning, whereas insulin increased progressively with age; the portal glucagon:insulin ratio, like hepatic carnitine, peaked soon after birth and fell with age. A multiple regression analysis indicated a positive association between glucagon and hepatic carnitine and a negative one between insulin and hepatic carnitine (R = 0.802, p = 0.001). An overall pattern of elevated dietary carnitine levels and increased small intestinal absorption and hepatic accumulation of carnitine is noted in early development. The finding of a similar pattern in glucagon-to-insulin ratio suggests that both hormones may participate in the regulation of enterohepatic carnitine distribution in newborns.
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PMID:Enterohepatic distribution of carnitine in developing piglets: relation to glucagon and insulin. 140 68

Ten epileptic children with chronic valproic acid (VPA) treatment were given L-carnitine for 14 days. As compared to age and sex matched control subjects the carnitine status of the VPA treated children showed carnitine insufficiency prior to the carnitine administration with lower total and free carnitine in plasma and in urine. In response to the extra intake the plasma free and esterified carnitines increased 1.7-fold. The daily excreted amount of esterified carnitines increased 6.5-fold (1.55 +/- 0.23 vs 10.1 +/- 1.68 mumol/kg/day, means +/- SEM, p less than 0.005) showing that a considerable part of the administered carnitine participated in the elimination of acyl groups from the body. The depressed level of beta-hydroxybutyrate in the plasma (31.8 +/- 7.42 vs controls 118.0 +/- 16.0 mumol/l, means +/- SEM, p less than 0.005) remained unaffected by the carnitine administration (29.7 +/- 7.06 mumol/l) suggesting that the hypoketonemia is not a direct consequence of the carnitine insufficiency. No differences were observed in the plasma level of free fatty acids, triglycerides and in insulin: glucagon ratios between the VPA treated and control subjects, suggesting that lipolysis of fats and the hepatic hormonal control mediated by these hormones are not the sites at which VPA causes reduced fasting ketogenesis. The plasma level of VPA and the seizure control remained unaffected by carnitine treatment.
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PMID:L-carnitine replacement therapy in chronic valproate treatment. 210 56

Carnitine palmitoyltransferase (CPT total) activity and synthesis increase in states where the insulin/glucagon ratio is low, such as starvation and diabetes [Brady & Brady (1987) Biochem. J. 246, 641-646]. However, the effect of glucagon and insulin on CPT synthesis is unknown. The present experiments were designed to determine the effect of glucagon, cAMP [8-(chlorophenylthio) cyclic AMP], and insulin + cAMP on CPT transcription and mRNA amounts over time after injection. The CPT protein that was purified, used to generate antibody, and cloned in these studies was the 68 kDa mitochondrial protein described previously [Brady & Brady (1987) Biochem. J. 246, 641-646; Brady, Feng & Brady (1988) J. Nutr. 118, 1128-1136; Brady & Brady (1989) Diabetes 38, in the press]. Saline-injected control rats exhibited a 2-fold increase in hepatic CPT transcription rate and CPT mRNA over the 5 h experiment from 09:00 to 14:00 h. The effect was most probably due to the fasting state of the rats during the day. Glucagon injection caused an 8-fold increase in transcription rate by 90 min and a 4-fold increase in CPT mRNA by 90-120 min. The cAMP effect had reached a peak by the first time point taken (15 min). Transcription rate was increased 4-fold and CPT mRNA was increased 3-fold at this time. The combination of cAMP + insulin injection did not produce any significant increase in transcription rate or CPT mRNA over the saline-injected controls. CPT mRNA and transcription rate showed a clear dose-response to glucagon injection from 0 to 150 micrograms/100 g body wt. Total CPT activity and immunoreactive CPT were not increased during these experiments. The data indicate that glucagon and insulin interact in control of transcription rate and amount of CPT mRNA, but that increases in CPT immunoreactive protein and activity are temporally delayed. This lag probably relates to the half-life of the CPT protein in vivo, which has been estimated as 2-7 days.
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PMID:Regulation of carnitine palmitoyltransferase in vivo by glucagon and insulin. 254 60

The authors report preliminary data on the behavior of some lipid fractions in cirrhosis of the liver and correlate them with the changes in the insulin, glucagon and C-peptide levels. Elevated FFA (Free Fatty Acids) and normal cholesterol, triglyceride and total lipid values indicate a prevalent insulin induced effect and a reduction of liver metabolism of these fractions. This hypothesis is supported by the fact that L-carnitine, which reestablishes the carnitine-dependent intracellular transport system, reduces the levels of all the lipid fractions studied. The normal C-peptide values in these patients with liver cirrhosis show that hyperinsulinemia is caused by impaired metabolism of this hormone and not by hyperincretion. This hyperinsulinemia seems to react positively to the improvement of the intracellular transport systems. A fall in the hyperglucagonemia follows the decreased hyperinsulinemia leading to a hormone balance with lower values and a consequent reduction of the hormonal stimuli on the lipid metabolism. The possibility of administering drugs, which can act on the metabolic pathways responsible for the high FFA plasma levels, which seem to play a role in the physiopathology of encephalopathies and hepatic coma is clinically interesting.
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PMID:[Plasma lipids, insulin, C-peptide, and glucagon levels in cirrhosis: personal observations]. 267 5

The effects of a single oral dose of carnitine on fasting-induced ketosis was investigated in four normal individuals, five patients with muscular dystrophy, and one patient with a generalized cytochrome c oxidase deficiency. Plasma carnitine, free fatty acids, glucose, insulin, and glucagon were also measured. Normal individuals showed an average 0.09 mM increase in blood beta-hydroxybutyrate concentration during a 12- to 18-hr period of fasting and carnitine administration did not affect this response (average: 0.12 mM). Muscular dystrophy patients showed a greater fasting-induced elevation in beta-hydroxybutyrate (average 0.29 mM) and carnitine administration greatly enhanced this ketogenic response (average 0.84 mM). The cytochrome c oxidase deficient patient showed an even larger increase in beta-hydroxybutyrate with fasting (1.67 mM) and carnitine further augmented this ketotic effect (3.78 mM). Plasma free fatty acids were also elevated in patients that showed enhanced ketosis. Plasma glucagon concentration did not change, but insulin levels decreased during the 12- to 18-hr period of fasting; no major differences were found between controls and patients. These results indicate that some patients with muscular dystrophy and cytochrome c oxidase deficiency are more prone to develop ketosis than normal individuals and that carnitine administration enhances this response. Since both muscular dystrophy patients and the patient with cytochrome c oxidase deficiency had similar ketogenic responses, the data suggest that ketone body utilization may be impaired in these patients. The ability of L-carnitine to be ketogenic should be considered in the treatment of these patients.
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PMID:Ketogenic effects of carnitine in patients with muscular dystrophy and cytochrome oxidase deficiency. 283 95

Activities (mumol X min-1 X g liver) and zonal distributions of key enzymes of carbohydrate metabolism were studied in livers of streptozotocin-diabetic rats and compared to the values in alloxan-diabetes. Streptozotocin led to a non-ketotic diabetes with blood glucose being increased by more than fivefold but ketone bodies being in the normal range, while alloxan produced a ketotic diabetes with blood glucose, acetoacetate and beta-hydroxybutyrate being elevated by more than fivefold. Portal insulin was decreased to about 20% in streptozotocin- and more drastically to about 7% in alloxan-diabetes. Conversely, portal glucagon was increased in the two states to about 250% and 180%, respectively. The glucogenic key enzyme phosphoenolpyruvate carboxykinase (PEPCK) was enhanced in streptozotocin- and alloxan-diabetes to over 300%, while the glycolytic pyruvate kinase L (PKL) was lowered to 65% and 80%, respectively. The normal periportal to perivenous gradient of PEPCK of about 3:1, as measured in microdissected tissue samples, was maintained with elevated activities in the two zones. The normal periportal to perivenous gradient of PKL of 1:1.7 was diminished with lowered activities in the two zones. The glucogenic glucose-6-phosphatase (G6Pase) was increased in streptozotocin- and alloxan-diabetes to 130% and 140%, respectively, while the glucose utilizing glucokinase (GK) was decreased to 60% and 50%, respectively. The normal periportal to perivenous gradient of G6Pase, demonstrated histochemically, remained unaffected. Carnitine palmitoyltransferase (CPT) was increased to over 190% and acetyl-CoA carboxylase (ACC) was decreased to 60% in streptozotocin, non-ketotic diabetes, while the two enzymes were altered more drastically to 400% and 50%, respectively, in alloxan, ketotic diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gluconeogenic-glycolytic capacities and metabolic zonation in liver of rats with streptozotocin, non-ketotic as compared to alloxan, ketotic diabetes. 302 62

A neonatal piglet model was used to study hepatic fatty acid metabolism during the early postnatal period. Hepatocytes were isolated from pigs at birth or after 24 h, in fed or unfed states (n = 4 pigs/group). Cells were incubated with 1 mmol/L [1-(14)C]-octanoate (C8) or -palmitate (C16) in the presence or absence of 1 mmol/L L-carnitine, carnitine plus tetradecylglycidic acid (TDGA; 10 mumol/L) or carnitine plus glucagon (0.5 microgram/L). Accumulation of radiolabel [nmol/(h. 10(6) cells)] in CO2 and acid-soluble products (ASP) was higher (3.5- and 4.5-fold, respectively) from C8 than from C16 (P < 0.0001). Glucagon, carnitine and TDGA had no effect on the oxidation of C8 (P > 0.1). Carnitine addition tended to increase C16 flux to ASP [from 5.3 to 7.6 nmol/(h. 10(6) cells); P < 0.1], whereas carnitine plus TDGA decreased flux (from 7.6 to 2.1; P < 0.001). Esterified products accounted for 70% of metabolized label in control C16 incubations; this was reduced to 62% by carnitine (P < 0.05) and increased to 80% by the addition of carnitine plus TDGA (P < 0.0001). The 1-(14)C flux to CO2 in cells from 24-h-old unfed piglets was 47% lower than from fed pigs (P < 0.01) but 28% higher than in pigs at birth. Radiolabel contained in ASP and total metabolized label were 48% lower from unfed pigs compared with the piglets at birth and 24-h-old fed pigs (P < 0.01) and were paralleled by changes in oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carnitine palmitoyltransferase modulation of hepatic fatty acid metabolism and radio-HPLC evidence for low ketogenesis in neonatal pigs. 756 89

Carnitine-deficient jvs mice expressed reduced levels of a group of genes which are preferentially expressed in the liver, including urea cycle enzyme genes (Biochim. Biophys. Acta 1138, 167-171, 1992). The expression of alpha-fetoprotein and aldolase A was elevated, indicating that the liver of jvs mice is undifferentiated or dedifferentiated (FEBS Lett. 311, 63-66, 1992). Studies of the hormone signal transduction pathway showed that serum cortisol and plasma glucagon levels of jvs mice were 2 and 3 times higher, respectively, than those of normal mice, and that the hormone binding activity of glucocorticoid receptor (GR) in the cytosol of jvs liver was 50% of normal mice, which reflected the amount of receptor protein in the cytosol. On the other hand, GR protein accumulated in the nuclear fraction in jvs mice. Exogenously administrated dexamethasone induced carbamoyl phosphate synthetase (CPS) and tyrosine aminotransferase (TAT) mRNAs in jvs mice, indicating that CPS and TAT genes in jvs mice are responsive to induction by glucocorticoid and cAMP. Analysis of transacting factors by gel retardation assay revealed that HNF-1, COUP-TF and SP-1 were detected at almost the same level in the hepatic nuclear fraction of jvs mice as in normal littermates, and C/EBP and CREB were a little higher in jvs mice, suggesting that these factors are probably not targets of jvs mutation causing abnormal gene expression in the liver. On the other hand, AP-1 binding activity was much higher in jvs mice from an early age, preceding the abnormal expression of urea cycle enzyme, and carnitine administration normalized AP-1 binding activity. We suggest that elevated AP-1 binding induced by carnitine deficiency is closely connected with the abnormal gene expression in the liver.
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PMID:Abnormal gene expression and regulation in the liver of jvs mice with systemic carnitine deficiency. 791 32

A double-blind crossover field study was performed to investigate the effects of acute L-carnitine supplementation on metabolism and performance of endurance-trained athletes during and after a marathon run. Seven male subjects were given supplements of 2 g L-carnitine 2 h before the start of a marathon run and again after 20 km of the run. The plasma concentration of metabolites and hormones was analysed 1 h before, immediately after and 1 h after the run, as well as the next morning after the run. In addition, the respiratory exchange ratio (R) was determined before and at the end of the run, and a submaximal performance test was completed on a treadmill the morning after the run. The administration of L-carnitine was associated with a significant increase in the plasma concentration of all analysed carnitine fractions (i.e. free carnitine, short-chain acylcarnitine, long-chain acylcarnitine, total acid soluble carnitine, total carnitine) but caused no significant change in marathon running time, in R, in the plasma concentrations of carbohydrate metabolites (glucose, lactate, pyruvate), of fat metabolites (free fatty acids, glycerol, beta-hydroxybutyrate), of hormones (insulin, glucagon, cortisol), and of enzyme activities (creatine kinase, lactate dehydrogenase). Moreover, there was no difference in the result of the submaximal performance test the morning after the run. In conclusion, acute administration of L-carnitine did not affect the metabolism or improve the physical performance of the endurance-trained athletes during the run and did not alter their recovery.
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PMID:Effects of L-carnitine supplementation on physical performance and energy metabolism of endurance-trained athletes: a double-blind crossover field study. 880 3

The carnitine carrier was investigated in S49 lymphoma cells, a murine cell type cultured in suspension culture and used widely in signal transduction studies. Carnitine uptake in S49 lymphoma cells was stimulated almost twofold by pretreatment of intact cells by 0.5 microM glucagon for 4 h. Plasma membranes derived from S49 lymphoma cells bound 556 +/- 81 pmol/mg protein whereas pretreatment by 0.5 microM glucagon for 4 h of cells, before cell harvesting and preparation of plasma membranes, increased the number of carnitine binding sites to 1196 +/- 52 pmol/mg protein. The glucagon pretreatment also altered the carnitine binding characteristics from a two site model to a single binding site. S49 lymphoma cells were further shown to contain 50.9 +/- 2.6 fmol glucagon receptors per 10(6) cells. We conclude that glucagon stimulated cellular uptake of carnitine by a mechanism that at least partially operated through increasing the number of available carnitine binding sites in plasma membranes.
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PMID:Glucagon increases cellular uptake and plasma membrane binding of L-carnitine in S49 lymphoma cells. 967 47


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