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)

The first goal of this study was to investigate whether totally pancreatectomized patients are glucagon deficient and if so, to what degree. Immunoreactive glucagon (IRG) concentrations in peripheral plasma of nine pancreatectomized patients were not significantly different from those of 10 normal controls as measured by two antisera (30-K and RCS-5) both detecting the COOH-terminal portion of the molecule and one (RCS-5) postulated to be specific for pancreatic glucagon. Plasma from six of nine pancreatectomized patients were fractionated over Sephadex G-50 and IRG was measured with both antisera in the column eluates. Using 30-K, 80.8 +/- 9% of the IRG eluted within the void volume. This material was rechromatographed on Sephadex G-200 and found to have an apparent mol wt of approximately 200,000. Only 18.3 +/- 9% eluted in the IRG3500 region. IRG3500 was significantly reduced in pancreatectomized patients as compared to normal controls (49 +/- 9 vs. 18 +/- 9 pg/ml, P less than 0.05). Using RCS-5, all IRG (corresponding to 20 +/- 6 pg/ml of plasma) eluted in the IRG3500 region. The second goal of this study was to investigate the effects of chronic glucagon deficiency on plasma amino acids. In the nine pancreatectomized patients studied, postabsorptive plasma concentrations of serine, alanine, arginine, glycine, threonine, citrulline, alpha-aminobutyrate, and tryosine were significantly elevated compared to values obtained from 20 normal controls. Physiological glucagon increments produced in two pancreatectomized patients by infusion of glucagon (6.25 and 8.0 microgram/h, respectively) resulted in normalization of the hyperaminoacidemia within 22 h. We conclude (a) that pancreatectomized patients are partially glucagon deficient because of diminished basal as well as diminished stimulated glucagon secretion; (b) that fasting concentrations of certain glucogenic amino acids are elevated in pancreatectomized patients probably as result of reduce; hepatic gluconeogenesis; and (c) that the RCS-5 antiserum is not "pancreatic glucagon" specific.
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PMID:Glucagon deficiency and hyperaminoacidemia after total pancreatectomy. 698 12

The artificial endocrine pancreas (AEP) can normalize glycemia at rest and with meals. To determine whether insulin, glucagon, and amino acid profiles are also normalized, nine diabetics on subcutaneous insulin (S/C) and AEP control were compared to ten normal controls (NC). Glycemia was monitored continuously over 10 hr during which meals were consumed. Insulin infusion rate, and the levels of immunoreactive insulin (IRI) (in NC), free insulin (in S/C and AEP), C-peptide, glucagon, and amino acids are reported. Glycemia in AEP started at somewhat higher levels than in NC, but with breakfast and thereafter, it was identical. In S/C, hyperglycemia prevailed throughout, with no systematic change in free IRI. In AEP, both basal and peak free insulin levels, measured in four patients, were significantly higher than in NC. C-peptide values were significantly lower in diabetics and did not change with meals. Basal glucagon values were not different in the three groups and changes with meals were of small magnitude. Branched chain amino acids were higher in S/C and did not increase as in NC. In AEP, levels were lower than NC after the first two meals. Similarly, lysine and threonine were lower in AEP than in NC at the same times. Alanine, though similar at the onset, was lower 2 hr postbreakfast and higher 2 hrs postsupper in AEP and S/C compared to NC. These studies demonstrate that glycemic control with AEP is accompanied by hyperinsulinemia, which could account for the amino acid responses and the small alterations in immunoreactive glucagon (IRG) patterns. Further refinement is needed to obtain full normalization of metabolic profiles.
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PMID:Insulin, glucagon, and amino acids during glycemic control by the artificial pancreas in diabetic man. 699 Jan 72

Insulin and glucagon have variable effects in altering arteriovenous differences for amino acids and glucose in liver and muscle. It has not been determined whether these hormones may similarly affect intestine. Acute effects of intraarterial insulin and glucagon were evaluated in in situ, luminally cleansed ileal segments in anesthetized, fasted dogs. Insulin significantly increased th ileal uptake of valine, isoleucine, leucine, tyrosine, threonine, and serine from arterial blood: uptake of these amino acids was approximately doubled 45 min after the end of the insulin infusion. Insulin had no effect on glucose uptake or release. Glucagon decreased ileal glutamate release into mesenteric venous blood 45 min after the end of infusion but the uptake or release of other amino acids and ammonia was not changed. Glucagon did increase mesenteric blood flow acutely and caused a net release of glucose into mesenteric venous blood. The results indicate that insulin and glucagon directly after metabolism of the ileum in vivo.
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PMID:Effects of insulin and glucagon on the uptake of amino acids from arterial blood by canine ileum. 700 41

Ammonium salts were infused in intact, pancreatectomized, and adrenalectomized dogs to produce coma-inducing amounts of plasma ammonia. Changes in intact dogs included hyperglycemia, hyperglucagonemia, hyperinsulinemia, and decreases in plasma concentrations of glutamine, alanine, threonine, glycine, lysine, valine, proline, serine, arginine, leucine, isoleucine, and methionine. Urinary excretion of catecholamines increased more than 20-fold, whereas plasma hydrocortisone concentrations were essentially unchanged. In pancreatectomized dogs, ammonia infusions caused hyperglycemia, a mild hyperglucagonemia, and no changes in plasma amino acid concentrations, other than a decrease in alanine and an increase in taurine. In adrenalectomized dogs, ammonia infusion resulted in normoglycemia, hyperglucagonemia (comparable with that seen in intact dogs), hyperinsulinemia (2 to 3 times that seen in intact dogs), and decreased plasma concentrations of alanine, isoleucine, leucine, and valine. Finally, propranolol administration did not affect ammonia-induced glucagon and insulin release. The endocrine portion of the pancreas appears to mediate the major effects of ammonia on plasma amino acid values. The effect of ammonia in stimulating glucagon release may occur by an alpha-adrenergic pathway or by direct stimulation of pancreatic islet cells.
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PMID:Effects of ammonia infusion on plasma glucagon, insulin, and amino acids in intact, pancreatectomized, and adrenalectomized dogs. 702 May

Hormonal regulation of L-serine dehydratase [L-serine hydro-lyase (deaminating), EC 4.2.1.13] was studied in primary cultures of adult-rat hepatocytes. The hepatocytes were isolated by collagenase perfusion and maintained in culture on collagen-gel/nylon-mesh substrata. L-Serine dehydratase activity was measured with [14C]threonine as substrate. The enzyme activity in hepatocytes of normal adult rats was low and declined rapidly in culture in L-15 medium containing 0.1 micro M-insulin and even more in the presence of glucose. L-Serine dehydratase activity in hepatocytes of rats with streptozotocin-induced diabetes was initially 20-fold higher than that of normal rats, but fell rapidly to a low value by 4 days in culture. Hormonal regulation of the enzyme activity was manifested by treatment of the cultured hepatocytes with insulin (0.1 micro M), glucagon (0.3 micro M), dexamethasone (10 micro M) and combinations of these hormones. Either glucagon or dexamethasone in the absence of insulin enhanced the activity of L-serine dehydratase, but failed to do so in the presence of insulin. Treatment with both hormones resulted in a 2-3-fold increase in enzyme activity in culture on days 3 and 4. Under conditions in which the enzyme activity was enhanced, glucose production by the cultured hepatocytes was concomitantly increased. Glucose production resulted in part from gluconeogenesis from pyruvate and not entirely from glycogenolysis. The gluconeogenic conditions of culture resulted in a decrease in cellular lipids in the cultured hepatocytes, as evidenced by ultrastructural studies.
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PMID:Increase of L-serine dehydratase activity under gluconeogenic conditions in adult-rat hepatocytes cultured on collagen gel/nylon mesh. 732 17

Proteins with seven transmembrane segments (7TM) define a superfamily of receptors (7TM receptors) sharing the same topology: an extracellular N-terminus, three extramembranous loops on either side of the plasma membrane, and a cytoplasmic C-terminal tail. Upon ligand binding, cytoplasmic portions of the activated receptor interact with heterotrimeric G-coupled proteins to induce various second messengers. A small group, recently recognized on the basis of homologous primary amino acid sequences, comprises receptors to hormones of the secretin/vasoactive intestinal peptide/glucagon family, parathyroid hormone and parathyroid hormone-related peptides, growth hormone-releasing factor, corticotropin-releasing factor, and calcitonin. A cDNA, extracted from a neuroectodermal cDNA library, was predicted to encode a new 886-amino-acid protein with three distinct domains. The C-terminal third contains the seven hydrophobic segments and characteristic residues that allow the protein to be readily aligned with the various hormone receptors in the family. Six egf-like modules, at the N-terminus of the predicted mature protein, are separated from the transmembrane segments by a serine/threonine-rich domain, a feature reminiscent of mucin-like, single-span, integral membrane glycoproteins with adhesive properties. Because of its unique characteristics, this putative egf module-containing, mucin-like hormone receptor has been named EMR1. Southern analysis of a panel of somatic cell hybrids and fluorescence in situ hybridization have assigned the EMR1 gene to human chromosome 19p13.3.
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PMID:EMR1, an unusual member in the family of hormone receptors with seven transmembrane segments. 760 60

The effect has been studied of various media, hormones and of amino acids on the membrane potential of rat hepatoma cells in culture measured by microelectrode impalement. Cells in Eagle's minimal essential medium plus 5% serum had a value which varied daily from about 5-8 mV, inside negative. The membrane potential of rat hepatocytes was measured to be 8.7 +/- 0.2 mV, inside negative. The membrane potential of the hepatoma cells was decreased by insulin and increased by glucagon. Membrane potential was unaffected by change of medium to Hanks' or Earle's balanced salt solutions or deprivation of serum. It was, however, reduced in cells in phosphate-buffered saline and by reduction of pH. The former effect was shown to be due to the higher [Na+] of phosphate-buffered saline as opposed to the other media. Addition of alanine, glycine, serine, proline and methylaminoisobutyrate all reduced membrane potential by 2-3 mV. Smaller decreases were seen with methionine, leucine and phenylalanine, but none with glutamine, threonine, BCH (2-aminonorborane-2-carboxylic acid) and D-alanine. The results are compared with the effects of similar conditions on aminoisobutyrate uptake. Whilst there was a correlation under some conditions there was not under others. It is concluded that for the hepatoma cells factors additional to the membrane potential must exert some influence on the capacity for amino acid transport.
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PMID:Membrane potential of rat hepatoma cells in culture: influence of factors affecting amino acid transport. 856 68

In pancreatic beta cells, cyclic AMP-dependent protein kinase regulates many cellular processes including the potentiation of insulin secretion. The substrates for this kinase, however, have not been biochemically characterized. Here we demonstrate that the glucose transporter GLUT2 is rapidly phosphorylated by protein kinase A following activation of adenylyl cyclase by forskolin or the incretin hormone glucagon-like peptide-1. We show that serines 489 and 501/503 and threonine 510 in the carboxyl-terminal tail of the transporter are the in vitro and in vivo sites of phosphorylation. Stimulation of GLUT2 phosphorylation in beta cells reduces the initial rate of 3-O-methyl glucose uptake by approximately 48% but does not change the Michaelis constant. Similar differences in transport kinetics are observed when comparing the transport activity of GLUT2 mutants stably expressed in insulinoma cell lines and containing glutamates or alanines at the phosphorylation sites. These data indicate that phosphorylation of GLUT2 carboxyl-terminal tail modifies the rate of transport. This lends further support for an important role of the transporter cytoplasmic tail in the modulation of catalytic activity. Finally, because activation of protein kinase A stimulates glucose-induced insulin secretion, we discuss the possible involvement of GLUT2 phosphorylation in the amplification of the glucose signaling process.
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PMID:Protein kinase A-dependent phosphorylation of GLUT2 in pancreatic beta cells. 862 92

Glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) and its own receptor have been found in the hypothalamus and brain stem of the rat. In an attempt to gain further insight into the role of this peptide in brain functioning we investigated the effects of GLP-1 (7-36)amide on the release of excitatory amino acid neurotransmitters by the ventromedial hypothalamus using an experimental microdialysis approach. GLP-1(7-36)amide produced an immediate increase in the extracellular concentrations of aspartic acid and glutamine, p < 0.01 and p < 0.05, respectively. By contrast, extracellular concentrations of glutamic acid, alanine, threonine, and tyrosine were unaffected. The results of this study show a stimulatory effect of GLP-1(7-36)amide on the release of aspartic acid and glutamine by the ventromedial hypothalamus of the rat.
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PMID:Glucagon-like peptide-1(7-36)amide induces the release of aspartic acid and glutamine by the ventromedial hypothalamus of the conscious rat. 866 66

The hormonal regulation of insulin-like growth factor binding protein (IGFBP)-1 and -4 mRNA was compared in serum-free primary rat hepatocyte cultures. The combination of dexamethasone and glucagon (Dex/Gluc) strongly increased IGFBP-1 and IGFBP-4 mRNA levels. Insulin suppressed Dex/Gluc-stimulated IGFBP-1 but not IGFBP-4 mRNA levels. In contrast, the peroxovanadium compound, bisperoxovanadium 1,10-phenanthroline (bpV(phen)), completely abrogated Dex/Gluc induction of both IGFBP mRNA species. Wortmannin and rapamycin blocked the inhibitory effect of insulin but not that of bpV(phen) on Dex/Gluc-stimulated IGFBP mRNA. Thus, although phosphatidylinositol 3'-kinase and p70s6k are necessary for insulin-mediated transcriptional inhibition of the IGFBP-1 gene, a signaling pathway, independent of phosphatidyloinositol 3'-kinase and p70s6k, is activated by bpV(phen) and mediates IGFBP-1 as well as IGFBP-4 mRNA inhibition. Mitogen-activated protein (MAP) kinase activity induced by insulin was suppressed to below basal levels in the presence of Dex/Gluc, whereas in response to bpV(phen), MAP kinase activity was high and unaffected by Dex/Gluc, consistent with a role of MAP kinases in bpV(phen)-mediated inhibition of IGFBP mRNA. The specific MAP kinase kinase (MEK) inhibitor, PD98059, inhibited insulin but not bpV(phen)-stimulated MAP kinase activity, suggesting that MAP kinases can be activated in a MEK-independent fashion. Peroxovanadium compounds are strong inhibitors of tyrosine phosphatases, which may inhibit specific tyrosine/threonine phosphatases involved in the negative regulation of MAP kinases.
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PMID:Phosphatidylinositol 3'-kinase and p70s6k are required for insulin but not bisperoxovanadium 1,10-phenanthroline (bpV(phen)) inhibition of insulin-like growth factor binding protein gene expression. Evidence for MEK-independent activation of mitogen-activated protein kinase by bpV(phen). 899 39


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