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)

Phosphorylation of fructose-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) by the catalytic subunit of cyclic AMP-dependent protein kinase from pig muscle decreased the K0.5 for fructose-bisphosphate from 21 to 11 microM. When the phosphorylated fructose-bisphosphatase was treated with trypsin the K0.5 increased to 22 microM. The K0.5 also increased when the phosphoenzyme was treated with a partially purified phosphatase from rat liver. There was no difference between the unphosphorylated and phosphorylated enzyme with respect to pH dependence, the pH optimum being about 7.0 for both. Limited treatment of fructose-bis-phosphatase with subtilisin, which cleaves the enzyme at its unphosphorylatable N-terminal part, increased the pH optimum more than limited treatment with trypsin, which releases the phosphorylated peptide at the C-terminal part of fructose-bisphosphatase. The phosphorylated site on the phosphorylated fructose-bisphosphatase was more easily split off by trypsin treatment than the corresponding unphosphorylated site. The results suggest in addition to the glucagon-induced phosphorylation of fructose-bisphosphatase described by Claus et al. [1] that the phosphorylation-dephosphorylation of fructose-bisphosphatase could be of importance for the hormonal regulation of the enzyme in vivo.
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PMID:The kinetics of unphosphorylated, phosphorylated and proteolytically modified fructose bisphosphatase from fat liver. 627 12

32P-labeled ATP-citrate lyase isolated from 32P-labeled hepatocytes treated with insulin contained 1.6-1.8-fold greater 32P-radioactivity per mg protein than control enzyme. Both enzyme preparations were digested in parallel with trypsin until 94% of all 32P-radioactivity was rendered acid soluble. Quantitative high performance liquid chromatographic peptide mapping of the tryptic digests revealed a principal 32P-peptide which accounted for at least 80% of the insulin induced increment in 32P-radioactivity of native lyase. This peptide was purified, sequenced, and the site of 32P-phosphorylation assigned by two methods: electrophoresis (pH 6.5) of residual peptide after each step of Edman degradation and solid phase sequencing. The site of insulin-directed phosphorylation of ATP-citrate lyase (Thr-Ala-Ser(32P)-Phe-Ser-Glu-Ser-Arg) is the same as that directed by glucagon, and, in turn, identical with that phosphorylated by the cAMP-dependent protein kinase in vitro.
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PMID:The insulin-directed phosphorylation site on ATP-citrate lyase is identical with the site phosphorylated by the cAMP-dependent protein kinase in vitro. 628 69

A growth hormone releasing factor of a human pancreatic islet tumor (hpGRF) of an acromegalic patient was purified and subjected to Edman degradation in a spinning cup sequencer. Approximately 0.7-1.2 nmol of peptide was applied to the cup without any pretreatment, after coupling to 3-sulfophenyl isothiocyanate or after cleavage with cyanogen bromide, staphylococcal protease, or trypsin. On the basis of the analytical data, the N-terminal sequence of 39 residues is established to be H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn- Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys- Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser- Asn-Gln-Glu-Arg-Gly-. It is proposed that alanine is residue 40 and represents (as free acid) the C terminus of hpGRF. Synthetic hpGRF(1-40)-OH is highly potent in stimulating GH secretion from the rat anterior pituitary in vitro and in vivo. The C-terminal sequence of hpGRF does not appear to contribute significantly to the biologic intrinsic activity and potency of hpGRF, as demonstrated by the fact that the natural product and the synthetic peptides hpGRF(1-40)-OH, hpGRF(1-40)-NH2, and hpGRF(1-29)-NH2 show equivalent in vitro activities. On the basis of sequence homologies, hpGRF is closely related to members of the glucagon secretin family, especially to the porcine gut peptide PHI.
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PMID:Sequence analysis of a growth hormone releasing factor from a human pancreatic islet tumor. 629 53

An islet cell tumor, characterized by proinsulin level significantly elevated above normal human pancreas, has been found to contain insulin- and glucagon-degrading activity. Examination by chromatography on Sephadex G-75 of the degradation products formed from insulin showed A chain, and B chain rich-A chain aggregate as previously found with rat pancreatic islets. There was, however, little conversion of A chain to low molecular weight components indicating that insulinoma peptidase that has been found to degrade glucagon at about pH 6.8 degraded that A chain to a markedly lower rate. In contrast to the insulin-degrading activity, which was activated by glutathione in the presence of EDTA, the peptidase activity was not affected by the thiol compound. The activity of the peptidase was markedly inhibited by chelating agents, i.e., EDTA and o-phenanthroline, whereas chymotrypsin and trypsin inhibitors, i.e., TOS-PheCH2Cl, TOS-LysCH2Cl, soybean and pancreas trypsin inhibitor were found to have no effect.
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PMID:Thiol-protein disulfide oxidoreductase and peptidase activities in insulinoma tissue. 632 44

[125I-Tyr10]Monoiodoglucagon [( 125I]MIG) was cross-linked to liver membrane glucagon receptors with hydroxysuccinimidyl-p-azidobenzoate, and the products were analyzed by sodium dodecyl sulfate-gel electrophoresis. Autoradiograms of the gel obtained after a 24-h exposure showed one major band at Mr = 63,000 that was sensitive to GTP and excess unlabeled glucagon. Exposure for 7 days showed labeling of an additional Mr = 33,000 species that was also sensitive to excess unlabeled glucagon. The Mr = 33,000 peptide can be obtained by subtilisin, trypsin, elastase, or Staphylococcus aureus V8 protease treatment of the [125I]MIG-occupied receptor in the membrane or in Lubrol-PX solution. In contrast, limited proteolysis of membranes containing vacant receptors results in labeling of a Mr = 24,000 peptide. The Mr = 24,000 peptide specifically binds [125I]MIG in a GTP-sensitive manner. The Mr = 33,000 peptide also retains GTP sensitivity since it releases bound [125I]MIG upon addition of GTP. Elastase treatment of the electroeluted Mr = 33,000 peptide yields the Mr = 24,000 and 15,000 fragments. The Mr = 15,000 peptide is the smallest fragment of the receptor as yet identified. Treatment of the Mr = 63,000 receptor with [125I]MIG cross-linked to it with endo-beta-N-acetylglucosaminidase F results in four distinct fragments with Mr values of 61,000, 56,000, 51,000, and 45,000; prolonged treatment resulted in the accumulation of the last two. Neither the Mr = 33,000 nor the Mr = 24,000 fragment appeared to be substrates for endo-beta-N-acetylglucosaminidase F. These data indicate that glucagon receptor is a glycoprotein of approximately 60,000 daltons which contains at least four N-linked glycans accounting for 18,000 daltons of its mass. Both its glucagon binding function and its capacity to interact with the stimulatory regulator of adenylyl cyclase are contained within a fragment of only approximately 21,000 daltons that does not contain any N-linked glycans. Hormone occupancy of the receptor results in a conformational change so as to expose a region that is susceptible to proteolysis by proteases of varying specificities to yield a peptide of approximately 30,000 daltons that also does not contain N-linked glycans.
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PMID:Structural analysis of the hepatic glucagon receptor. Identification of a guanine nucleotide-sensitive hormone-binding region. 632 24

The biosynthesis of insulin, in particular the occurrence of a proinsulin-like molecule (PILM), in the pancreas of the green anole, Anolis carolinensis, was investigated. The laboratory rat was used for comparison and validation of the procedures. Anolian pancreases were incubated in vitro with radiolabeled leucine or proline. Radioactivity incorporated into the acidic ethanol-soluble (AES) phase increased in an essentially linear manner with time. Selective incorporation of labeled amino acids into AES material was not enhanced by a high concentration of glucose (6 mg/ml), by the addition of glucagon, which increases cyclic AMP levels, or by the addition of cytochalasin B; yet all three conditions result in stimulated insulin secretion. Gel filtration of the AES material on columns of Bio-Gel P-30 revealed a major peak of radioactivity whose apex followed closely the apogee of porcine proinsulin. When this presumptive PILM was treated with trypsin and carboxypeptidase B, the radioactivity was shifted towards later elution volumes, but the peak of the converted anolian material was not coincidental with marker insulin. Immunopurification techniques and additional molecular filtrations resulted in the isolation of fractions with both insulin-like immunoreactivity (IRI) and radioactivity derived from tritium-labeled leucine. One peak of radiolabel was present in the region of the proinsulin standards. The level of radioactivity in the region of the insulin standards was relatively high after two days of organ culture of splenic pancreases. By polyacrylamide gel electrophoresis proteins that incorporated radiolabeled amino acids and had insulin-like immunoreactivity possessed migration patterns similar to those of mammalian proinsulin and insulin. The insulin-like component was less readily demonstrated than the proinsulin-like component and raises the possibility that anolian PILM may be a major storage form in this species. The results are consistent with the synthesis of a proinsulin-like precursor in the beta cells of the green anole. The results also provide evidence for a precursor-product relationship in the anolian beta cell.
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PMID:Biosynthesis of a proinsulin-like molecule in the pancreas of a lizard. 635 1

Well-preserved pancreatic islet cell suspensions were prepared from islets of Langerhans of neonatal rats by gentle trypsin treatment. Within a culture period of 4-6 days the islet cells reaggregate spontaneously and form pseudo-islets of different size and of a variable insulin content. While the ratio of insulin to glucagon in isolated islets of Langerhans is constant (18 +/- 1.9), the hormone ratio of the pseudo-islets is strongly variable and increased, indicating an excess of insulin. Glucose enhancement from 1.5 mmoles/l to 15 mmoles/l results in a significant stimulation of (pro)insulin biosynthesis whereas insulin secretion of the pseudo-islets is only slightly increased. At high glucose concentration (15 mmoles/l) insulin secretion of the pseudo-islets can be potentiated (by a factor of 4.5 +/- 0.46) by 3-isobutyl-l-methylxanthine (IBMX). Compared with the initial islet cell suspension, the cell aggregation during pseudo-islet formation did not result in an enhanced secretory response on glucose stimulation.
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PMID:Characterization of pseudo-islets formed from pancreatic islet cell suspensions of neonatal rats. 635 94

A cholesterol-binding protein was previously isolated from human pancreas [Sziegoleit (1982) Biochem. J. 207, 573-582] and shown to consist of a single polypeptide chain with an apparent Mr of 28 000 and an isoelectric point of pH 4.9. In further investigations, a proteolytic activity was observed to be present in preparations of this protein. The enzyme activity was not dissociable from the cholesterol-binding protein. It decreased in the presence of sodium dodecyl sulphate or urea parallel to degradation of the protein, indicating autodegradation in the presence of these denaturants. Glucagon digestion studies indicated the carbonyl bond of alanine to be a favoured site of the enzymic cleavage. The proteinase was inactive against chromogenic substrates relatively specific for elastase, trypsin and chymotrypsin, but was found to cleave benzyloxycarbonylalanine p-nitrophenyl ester efficiently. The enzyme was inactivated by phenylmethanesulphonyl fluoride and was thus classified as a serine proteinase. Autoradiographic studies demonstrated binding to serum alpha 1-antitrypsin and alpha 2-macroglobulin in a similar manner to that observed with other pancreatic endo-proteinases. The collective results indicate that the isolated protein, provisionally named 'cholesterol-binding pancreatic proteinase', is a novel proteinase of the human pancreas. Quantitative measurements indicate that it comprises 4-6% of total protein in pancreatic secretions.
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PMID:A novel proteinase from human pancreas. 637 80

Fetal hepatocytes isolated at day 22 of gestation by trypsin digestion of rat liver retain their responsiveness to hormones. Glucagon significantly stimulates glycogenolysis and glucose release to 115 and 124%, respectively. The effect of alpha- and beta-agonists is more pronounced enhancing glycogen breakdown and glucose release to 133 and 147% (L-phenylephrine) and 183 and 202% (isoproterenol), respectively. The isolated fetal hepatocytes obtained by trypsin digestion are a useful tool for studying the hormonal control of liver metabolism during the perinatal stage without limitations met otherwise with extrahepatic factors and the effect of altered blood flow.
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PMID:Effect of glucagon, phenylephrine, and isoproterenol on glycogenolysis and glucose release from fetal rat hepatocytes in suspension. 662 25

The present study demonstrates an inhibitory effect of glucagon on the adenylate cyclase system of rabbit heart. Inhibition was maximal (22-40%) at 0.1-0.01 microM glucagon and required the presence of 0.01-0.1 mM GTP or guanosine 5'-[beta, gamma-imido]triphosphate (GuoPP[NH]P). Reduced or no inhibitor effect of glucagon was observed: (a) after limited proteolysis of plasma membrane proteins by trypsin, (b) in the presence of 1 mM Mn2+, (c) in the absence of Na+, and (d) during the first 10 min of incubation if GuoPP[NH]P was the activating ligand. With GTP as the activating ligand, inhibition of cyclase by glucagon occurred without delay. These data are consistent with a mediation of glucagon inhibition by a guanine-nucleotide-binding protein. In the presence of ethanol (0.2 M) or benzyl alcohol (0.05 M), agents which are known to increase the fluidity of biological membranes, glucagon increased the enzyme activity in a guanine-nucleotide-dependent manner. Activation of cyclase in the presence of alcohols was maximal (30-60%) at 0.1-1.0 microM glucagon and 0.01 mM guanine nucleotides. Data suggest that glucagon receptors can interact with both the activatory and inhibitory guanine-nucleotide-binding proteins and the physical state of membranes may play a role in determining which interaction will be preferential.
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PMID:Guanine-nucleotide-dependent inhibition of adenylate cyclase of rabbit heart by glucagon. 674 78


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