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)

To evaluate the effect of caloric restriction and dietary composition on circulating T3 and rT3 obese subjects were studied after 7-18 days of total fasting and while on randomized hypocaloric diets (800 kcal) in which carbohydrate content was varied to provide from 0 to 100% calories. As anticipated, total fasting resulted in a 53% reduction in serum T3 in association with reciprocal 58% increase in rT3. Subjects receiving the no-carbohydrate hypocaloric diets for two weeks demonstrated a similar 47% decline in serum T3 but there was no significant change in rT3 with time. In contrast, the same subjects receiving isocaloric diets containing at least 50 g of carbohydrate showed no significant changes in either T3 or rT3 concentration. The decline in serum T3 during the no-carbohydrate diet correlated significantly with blood glucose and ketones but there was no correlation with insulin or glucagon. We conclude that dietary carbohydrate is an important regulatory factor in T3 production in man. In contrast, rT3 concentration is not significantly affected by changes in dietary carbohydrate. Our data suggest that the rise in serum rT3 during starvation may be related to more severe caloric restriction than that caused by the 800 kcal diet.
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PMID:Effect of caloric restriction and dietary composition of serum T3 and reverse T3 in man. 124 90

A reduction in the release of substrate amino acids from skeletal muscle largely explains the decrease in gluconeogenesis characterizing prolonged starvation. Brief starvation is associated with an increase in gluconeogenesis, suggesting increased release of amino acids from muscle. In the present studies, accelerated amino acid release from skeletal muscle induced by brief starvation was sought to account for the accompanying augmentation of gluconeogenesis. To do this amino acid balance across forearm muscles was quantified in 15 postabsorptive (overnight fasted) subjects and in 7 subjects fasted for 60 h. Fasting significantly reduced basal insulin (11.3-7.5 muU/ml) and increased glucagon (116-134 pg/ml). Muscle release of the principal glycogenic amino acids increased. Alanine release increased 59.4%. The increase in release for all amino acids averaged 69.4% and was statistically significant for threonine, serine, glycine, alanine, alpha-aminobutyrate, methionine, tyrosine, and lysine. Thus, with brief starvation, muscle release of glycogenic amino acids increases strikingly. This contrasts with the reduction of amino acid release characterizing prolonged starvation. The adaptation of peripheral tissue metabolism to brief starvation is best explained by the decrease in insulin.
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PMID:Effects of brief starvation on muscle amino acid metabolism in nonobese man. 125 28

Distribution ratios (intracellular concn/extracellular concn) of alpha-amino isobutyric acid (AIB) after intravenous injection were determined in fed, 12-h, 1-day, and 5-day starved rats. Progressive increases (over fourfold) in the distribution ratios of AIB in the liver and progressive decreases (over threefold) in the gastrocnemius muscle occurred within these periods. On full day of protein deprivation was without effect on AIB distribution ratios, but after 5 days it produced an increased distribution ratio of AIB in the liver (twofold), without affecting that of the muscle. A sudden increase in hepatic glucose output, induced by phlorizin, was followed by an increase in the liver distribution ratio of AIB. In starvation the increase in plasma concentration of glucagon and decrease in insulin level preceded the changes in AIB distribution ratios; in protein deprivation there was no change in plasma concentrations of these hormones. It is concluded that caloric restriction profoundly affects amino acid transport by the liver and by the skeletal muscle. These transport changes would enhance the availability of substrates for increased gluconeogenesis during starvation.
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PMID:Dietary regulation of liver and muscle transport of amino acid. 125 99

Plasma lipid and hormone levels have been measured during 72 hours total starvation in nine healthy subjects, to assess the relative importance of hormones and substrates in human triglyceride metabolism. Plasma free fatty acid and glycerol concentrations rose steadily on each day of starvation. Plasma triglyceride concentrations rose on the second and third days, from a control level of 649 +/- 67 mg/1 to a maximum of 1001 +/- 66 mg/1. Plasma cholesterol concentrations remained unchanged while glucose concentrations fell and insulin did not change. Plasma glucagon (C-GLI) levels doubled while secretin levels, reported previously, rose threefold. It is suggested that during acute starvation the rise in triglyceride concentration results from the increased availability of free fatty acids, and that elevated secretin and glucagon levels enhance lipolysis and hence provide substrates for triglyceride synthesis.
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PMID:Triglyceride metabolism in acute starvation: the role of secretin and glucagon. 126 85

Periportal and perivenous hepatocytes possess different amounts and activities of the rate-generating enzymes of carbohydrate and oxidative energy metabolism and thus different metabolic capacities. This is the basis of the model of metabolic zonation, according to which periportal cells catalyze predominantly the oxidative catabolism of fatty and amino acids as well as glucose release and glycogen formation via gluconeogenesis, and perivenous cells carry out preferentially glucose uptake for glycogen synthesis and glycolysis coupled to liponeogenesis. The input of humoral and nervous signals into the periportal and perivenous zones is different; gradients of oxygen, substrates and products, hormones and mediators and nerve densities exist which are important not only for the short-term regulation of carbohydrate metabolism but also for the long-term regulation of zonal gene expression. The specialization of periportal and perivenous hepatocytes in carbohydrate metabolism has been well characterized. In vivo evidence is provided by the complex metabolic situation termed the 'glucose paradox' and by zonal flux differences calculated on the basis of the distribution of enzymes and metabolites. In vitro evidence is given by the different flux rates determined with classical invasive techniques, e.g. in periportal-like and perivenous-like hepatocytes in cell culture, in periportal- and perivenous-enriched hepatocyte populations and in perfused livers during orthograde and retrograde flow, as well as with noninvasive techniques using miniature oxygen electrodes, e.g. in livers perfused in either direction. Differences of opinion in the interpretation of studies with invasive and noninvasive techniques by the authors are discussed. The declining gradient in oxygen concentrations, the decreasing glucagon/insulin ratio and the different innervation could be important factors in the zonal expression of the genes of carbohydrate-metabolizing enzymes. While it is clear that the hepatocytes sense the glucagon/insulin gradients via the respective hormone receptors, it is not known how they sense different oxygen tensions; the O2 sensor may be an oxygen-binding heme protein. The zonal separation of glucose release and uptake appears to be important for the liver to operate as a 'glucostat'. Thus, zonation of carbohydrate metabolism develops gradually during the first weeks of life, in part before and in part with weaning, when (in rat and mouse) the fat- and protein-rich but carbohydrate-poor nutrition via milk is replaced by carbohydrate-rich food. Similarly, zonation of carbohydrate metabolism adapts to longer lasting alterations in the need of a 'glucostat', such as starvation, diabetes, portocaval anastomoses or partial hepatectomy.
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PMID:Hepatocyte heterogeneity in the metabolism of carbohydrates. 128 81

Autophagic vacuoles (AVs) arise when membranes of the ER sequester parts of the cytoplasm, forming a new, double-membraned vacuole, to which lysosomal enzymes are then delivered. To investigate the mechanism of lysosomal enzyme delivery to nascent AVs, amino acid (AA) starvation and glucagon treatment were used to induce autophagy in a cultured cell system using rat hepatocytes (Fu5C8 cells). The induction of autophagy was assayed using biochemical, morphometric and immunocytochemical techniques. In these cells, AA starvation resulted in a fivefold increase in total cellular proteolysis, and sixfold and 4.5-fold increases in the volume and surface densities of AVs, respectively. Using an antibody against the mannose 6-phosphate receptor (MPR) and two sizes of colloidal gold to label separately and track the endosomal and lysosomal compartments, the time course of endosomal and lysosomal fusion with AVs was analyzed in detail. On the basis of these experiments, we found that AVs rapidly fuse with pre-existing lysosomes, but seldom with a prelysosomal compartment (PLC). Using immunoperoxidase, staining for the MPR was infrequently observed in association with any AVs. However, at early times following the induction of autophagy (less than 2 h), many autophagic vacuoles stained positively for the lysosomal enzyme cathepsin D. Consistent with these results, treatment of cells with tunicamycin had no effect on autophagy-induced proteolysis. We conclude that lysosomal enzyme delivery to nascent AVs occurs primarily by the fusion of pre-existing mature lysosomes, with a much smaller contribution by MPRs or the PLC.
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PMID:Autophagic vacuoles rapidly fuse with pre-existing lysosomes in cultured hepatocytes. 132 48

There is increasing evidence that membrane transporters for glutamine and glutamate are involved in control of liver metabolism in health and disease. We therefore investigated the effects of three catabolic states [starvation (60 h), diabetes (4 days after streptozotocin treatment) and corticosteroid (8-day dexamethasone) treatment] associated with altered hepatic amino acid metabolism on the activity of glutamine and glutamate transporters in sinusoidal membrane vesicles from livers of treated rats. In control preparations, L-[14C]glutamine uptake was largely Na(+)-dependent, but L-[14C]glutamate uptake was largely Na(+)-independent. Vmax. values for Na(+)-dependent uptake of glutamine and/or glutamate exceeded control values (by about 2- and 12-fold respectively) in liver membrane vesicles from starved (glutamine), diabetic (glutamate) or steroid-treated (glutamine and glutamate) rats. The Km values for Na(+)-dependent transport of glutamine or glutamate and the rates of their Na(+)-independent uptake were not significantly altered by any treatment. Na(+)-independent glutamate uptake appeared to include a dicarboxylate-exchange component. The patterns of inhibition of glutamine and glutamate uptake by other amino acids indicated that the apparent induction of Na(+)-dependent amino acid transport in catabolic states included increased functional expression of systems A, N (both for glutamine) and X-ag (for glutamate). The results demonstrate that conditions resulting in increased secretion of catabolic hormones (e.g. corticosteroid, glucagon) are associated with increased capacity for Na(+)-dependent transport of amino acids into liver cells from the blood. The modulation of hepatic permeability to glutamine and glutamate in these situations may control the availability of amino acids for intrahepatic metabolic processes such as ureagenesis, ammonia detoxification and gluconeogenesis.
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PMID:Transport of L-glutamine and L-glutamate across sinusoidal membranes of rat liver. Effects of starvation, diabetes and corticosteroid treatment. 135 Sep 2

Glucagon treatment of fed rats (50 micrograms I.P. every 6 h for 3 days) induces significant increases in vitro of the basal short-circuit currents of the jejunum (52%) and proximal ileum (81%) and in their electrogenic secretory responses to stimulation by bethanechol, a muscarinic agonist. The results support a role for glucagon in the intestinal hypersecretion observed in starvation and nutrient deprivation.
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PMID:Enhanced electrogenic secretion in vitro by small intestine from glucagon-treated rats: implications for the diarrhoea of starvation. 135 76

To determine whether starvation affects the metabolism of glucagon-like peptide-1 (GLP-1), we measured the plasma levels of proglucagon-derived peptides and the biosynthesis and posttranslational processing of proglucagon in groups of six rats starved for 1, 3 and 5 days. The plasma levels of GLP-1 immunoreactivity (GLP-1 IR) and glucagon-like immunoreactivity (GLI) decreased during starvation reaching 79 and 56% of the respective control values by day 5 (P less than 0.05 and less than 0.01 vs control). The same is true of the plasma IRI level. The ileal contents of GLP-1 IR and GLI were 50.8 +/- 3.8 pmol/g wet weight and 161.8 +/- 13.2 pmol/g wet weight, respectively, on day 5 of starvation, which were significantly lower (P less than 0.01) than the respective values of 94.8 +/- 16.6 pmol/g wet weight and 262.7 +/- 28.1 pmol/g wet weight in control rats. However, the pancreatic contents of proglucagon-derived peptides tended to increase during starvation, although their increases were not statistically significant. No significant change in the posttranslational processing of proglucagon was detected during starvation. The decrease in the ileal proglucagon-derived peptides content was not associated with a decrease in intestinal proglucagon mRNA transcripts. These results suggested that decreased synthesis of proglucagon-derived peptides by the intestine was largely responsible for the reductions in their circulating levels in starved rats.
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PMID:Decrease in plasma GLP-1 immunoreactivity in starved rats. 137 10

Key enzymes related to lipogenesis in the liver are induced by a high glucose diet or insulin and suppressed by starvation, diabetes, or glucagon. Most of these enzymes are also induced by dietary fructose, even in diabetic liver. This regulation occurs at the posttranscriptional level as well as at the transcriptional level. We studied extensively the molecular mechanism of induction of L-type pyruvate kinase (LPK). The transcription of the LPK gene in the liver was stimulated by insulin and inhibited by glucagon. This insulin action required ongoing protein synthesis and metabolism of glucose and was enhanced by glucocorticoid. On the other hand, the mechanism of induction of the LPK by dietary fructose depended on plasma insulin levels. Dietary fructose stimulated transcription of the LPK gene in normal rats, whereas it acted mainly at the posttranscriptional level in diabetic rats. These fructose effects were attributable to a common metabolite of fructose and glycerol. The induction of LPK mRNA by dietary glucose was impaired in the liver of Wistar fatty rats, a model of obese non-insulin-dependent diabetes mellitus, but fructose-induced accumulation of the mRNA was not. Studies on transgenic mice indicated that the 5'-flanking region up to -3 kb of the LPK gene contained all cis-acting elements necessary for tissue-specific expression of LPK and its stimulation by diets and insulin. Further analysis using a transient expression assay revealed the presence of three cis-acting elements necessary for expression of LPK in hepatocytes in the region up to -170 kb. However, these elements alone were not sufficient for dietary and hormonal regulation of this enzyme when analyzed in transgenic mice.
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PMID:Molecular mechanism of induction of key enzymes related to lipogenesis. 157 84


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