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)

Rats were given soybean trypsin inhibitor or repeatedly injected with pancreozymin (daily 40 I.D.U./kg) for 7 days, and the insulin and glucagon contents of the pancreas were measured. The insulin and glucagon contents were markedly increased after these treatments and this effect was especially conspicuous after injections of large doses (daily 120 I.D.U.) of depot-type pancreozymin. Insulin content thus reached 1.9 times, and glucagon content 2.4 times as much in control values. This result is compatible with our previous histological finding that not only the exocrine pancreas but also islet cells undergo the trophic effect of endogenous and exogenous pancreozymin.
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PMID:Effects of oral administration of trypsin inhibitor and repeated injections of pancreozymin on the insulin and glucagon contents of rat pancreas. 43

1. Rat livers were dissociated into their constituent cells by perfusion through the portal vein with a medium containing collagenase, and hepatocytes separated from non-parenchymal cells. 2. It is shown that the procedure described by Wisher & Evans [(1975) Biochem. J. 146, 375-388] for preparation of plasma membranes from liver tissue when applied to isolated hepatocytes also yielded subfractions of similar morphology and marker-enzyme distribution. 3. Thus the distribution of alkaline phosphodiesterase, 5'-nucleotidase and the basal and glucagon-stimulated adenylate cyclase among two 'light' vesicular and one 'heavy' junction-containing plasma-membrane subfractions paralleled that reported for tissue-derived plasma-membrane subfractions. 4. Increased recoveries and specific activities of plasma-membrane marker enzymes were obtained when soya-bean trypsin inhibitor was included in the collagenase-containing perfusion media used to dissociate the liver. 5. Polyacrylamide-gel-electrophoretic analysis of the corresponding plasma-membrane subfractions prepared from liver tissue and isolated hepatocytes were generally similar. 6. The results indicate that the functional polarity of the hepatocyte's plasma membrane is retained after tissue dissociation. The damage occurring to plasma-membrane ectoenzymes by the collagenase-perfusion procedure is discussed.
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PMID:Preparation of plasma-membrane subfractions from isolated rat hepatocytes. 88 Feb 46

Tryptophanyl peptide bonds are selectively cleaved by N-chlorosuccinimide (NCS) under acidic conditions. All other peptide bonds are resistant to cleabage by this reagent. Optimal conditions for cleavage are: 2 equiv of NCS, pH 4-5, or 50-80% acetic acid for 30 min at room temperature. Under these conditions methionine residues are oxidized to methionine sulfoxides and cysteine. Other amino acids are not modified. The cleavage reaction was studied with several peptides containing tryptophan residueas successfully applied to several proteins. In alpha-lactalbumin, Kunitz trypsin inhibitor ,and apomyoglobin, selective cleavage of the expected tryptophanyl peptide bonds was obtained in 19-58% yield. The glucagon molecule was fragmented into two peptides in 32% yield.
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PMID:Selective chemical cleavage of tryptophanyl peptide bonds by oxidative chlorination with N-chlorosuccinimide. 99 Feb 66

Interactions of several proteins with glutathione-insulin transhydrogenase (GIT) have been investigated by determining their ability to inhibit degradation of 125I-labeled insulin catalyzed by GIT. The inhibition by every insulin analog (des-Asn-des-Ala-pork insulin, desoctapeptide-pork insulin, des-Ala-pork insulin, pork insulin, proinsulin, and guinea pig insulin) was competitive vs. competitive vs. insulin indicating that they function as alternate substrates. The insulin analogs with the least hormonal activity showed the highest potency as inhigitors of insulin degradation. Whereas native ribonuclease and lysozyme showed little or no inhibition, their scrambled forms (i.e. reduced and randomly reoxidized) showed competitive inhibition with a potency greater than that of insulin. These results suggest that the conformation of the substrate or inhibitor is probably the major factor in determining the specificity for (or binding to) the enzyme. Studies withother peptide hormones showed competitive inhibition with vasopressin and oxytocin and noncompetitive inhibition with glycagon. The inhibition with growth hormone could be either competitive or noncompetitive. The inhibition by glucagon and growth hormone (physiologic antagonists of insulin) could serve as a control mechanism to modulate the activity of enzyme. The following showed very little or no inhibition; the native and scrambled form of pepsinogen, trypsin inhibitor of beef pancreas and of lima bean, C-peptide of pork proinsulin, and heptapeptide (B23-B29) of insulin.
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PMID:Interaction of insulin analogs, glucagon, growth hormone, vasopressin, oxytocin, and scrambled forms of ribonuclease and lysozyme with glytathione-insulin transhydrogenase (thiol: protein-disulfide oxidoreductase): dependence upon conformation. 117 Aug 77

1. Plasma concentrations of insulin, C-peptide, glucagon and glucose were measured in surgically pancreatectomized pigs given insulin into the colon directly and in enteric peptidase-resistant (methacrylic acid copolymer-encapsulated) form. 2. Following introduction of insulin-containing capsules, plasma insulin concentration rose from 2.7 +/- 0.1 microU/ml to 110.9 +/- 51.9 microU/ml in the portal vein, and from 2.6 +/- 0.1 microU/ml to 26.9 +/- 7.3 microU/ml in the systemic circulation. Corresponding portal and systemic values after direct (non-encapsulated) insulin instillation were 28.2 +/- 15.9 microU/ml to 44.8 +/- 13.0 microU/ml and 7.5 +/- 2.6 microU/ml to 15.2 +/- 2.5 microU/ml respectively. Insulin concentrations peaked at 75 min in the group as a whole and between 60-90 min in individual animals. Absorption was most pronounced in pigs given aprotinin (a trypsin inhibitor) with insulin. 3. Plasma portal vein glucose concentrations fell from 76.2 +/- 8.9 mg/dl to 31.1 +/- 3.2 mg/dl 150 min after encapsulated insulin administration. Corresponding systemic glucose levels were 84.5 +/- 11.0 mg/dl and 37.0 +/- 1.4 mg/dl. 4. Colonic administration of insulin in methacrylic acid coated capsules results in peak portal and systemic insulin levels 60-90 min after administration. Co-administration of aprotinin enhances the fraction of insulin absorbed.
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PMID:Effective portal insulin delivery with enzyme-protected capsules in pancreatectomized pigs. 137 71

Isolation and culture techniques for hepatocytes from whole livers of the cynomolgus monkey, Macaca fascicularis, are described. Hepatocytes were isolated by two-step perfusion of livers, using collagenase with hyaluronidase; fructose and trypsin inhibitor were included to reduce cell loss. Yields from a single liver average 4 X 10(9) cells with viabilities of 90.8 +/- 5.7%. Cells, plated on collagen substrates, were assessed for changes in morphology and various marker enzyme activities over a period of 7 d in culture. Cells exhibited a morphology similar to that observed for this species in vivo; little change in attached and spread cells was observed over the length of time monitored. Enzyme activities for catalase, succinate dehydrogenase, and tyrosine aminotransferase were observed to decrease significantly (though considerable activity remained), whereas acid phosphatase and 5'-nucleotide phosphodiesterase remained unchanged. Activity of cytochrome P-450 reductase was observed to increase slightly for the first 2 d, then decrease to about 60% of initial levels. Activity of alpha-mannosidase was stable for 4 d but was observed to be increased at Day 7. Cells were observed to retain metabolic responsiveness, demonstrated by glucose production by both gluconeogenesis and glycogenolysis in response to glucagon stimulation. The monkey hepatocytes obtained by methods described here thus retain hepatocellular morphology and activity through at least 1 wk in culture without medium or culture modification.
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PMID:Isolation and culture of hepatocytes from the cynomolgus monkey (Macaca fascicularis). 197 77

Regulation of endocrine pancreatic hormone gene expression by cholecystokinin (CCK) was examined in the rat using cloned cDNA probes to quantify changes in specific mRNAs (insulin, glucagon, pancreatic polypeptide and somatostatin). Plasma CCK levels were raised to concentrations comparable to physiologic postprandial values either by including soybean trypsin inhibitor (SBTI) in the intraduodenal perfusate of an elemental diet (6.9 +/- 1.0 pM, n = 6), or by intravenous infusion of CCK-8 (6.0 +/- 0.9 pM, n = 6). SBTI infusion for 48 h resulted in a three- to fourfold increase in procarboxypeptidase B and kallikrein mRNA levels. Similar increases were observed when CCK was infused intravenously for 24 h. In contrast, neither SBTI intraduodenally, nor intravenous CCK had any effects on mRNA levels of insulin, glucagon, PP or somatostatin. These data therefore indicate that CCK at physiologic postprandial plasma concentrations stimulates pancreatic protease gene expression but has no effects on gene expression of endocrine pancreatic hormones.
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PMID:Effects of CCK on gene expression of endocrine pancreatic hormones. 226 71

Cathepsin-D has been previously reported to cleave intact PTH into PTH-(1-34) and -(35-84) in membranous fractions of rat and bovine kidney. Whether PTH degradation occurs by intact kidney cells, however, has not been examined in detail. We have, therefore, examined this possibility using an opossum kidney (OK) cell line which possesses the characteristics of proximal renal tubules and responds to PTH. PTH radioimmunoreactivity recovered in trichloroacetic acid-soluble products and in fractions eluted from reverse phase HPLC was measured using an antibody directed to the midregion and C-terminus of PTH. In this study, intact OK cells, but not extracellular enzymes, cleaved human (h) PTH-(1-84) into three discrete fragments which were released into the medium in a time- and temperature-dependent fashion. Half-maximal velocity of PTH-degrading activity (PTHDA) was observed at 9 nM hPTH-(1-84). A 1000-fold molar excess of PTH antagonists [hPTH-(3-34) and [Tyr34]hPTH-(7-34)amide] markedly inhibited PTHDA, whereas ACTH, glucagon, or big gastrin did not suppress it, suggesting an involvement of the PTH receptor in PTHDA. This PTHDA was strongly inhibited by phenylmethylsulfonylfluoride and chymostatin, but not by trypsin inhibitor, elastatinal, or inhibitors of aspartic, cysteine, or metalloproteinases, suggesting that it is due to a seryl chymotrypsin-like endopeptidase. Analysis of chymotrypsin-digested products of hPTH-(1-84) eluted from HPLC exhibited five fragments detected by UV absorbance (210 nm), three of which were measurable by PTH RIA, and each corresponded to the three PTH fragments produced by OK cells. All three fragments were predominantly suppressed in the presence of chymostatin, suggesting that chymotrypsin-like activity is solely responsible for PTHDA in intact OK cells. To further explore the cleavage sites of PTH by chymotrypsin, amino acid analysis of chymotrypsin-cleaved products was performed. The results strongly support the conclusion that a chymotrypsin-like enzyme in OK cells cleaved the hormone between residues 23-24, and 34-35 to produce, at least, hPTH-(24-84) and -(35-84). Lysosomal blockers (chloroquine, ammonium chloride, or monensin) did not affect this PTHDA. Our present study indicates that chymotrypsin-like endopeptidase, but not other endopeptidase or lysosomal enzymes, is responsible for the limited hydrolysis of PTH by intact OK cells.
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PMID:Parathyroid hormone degradation by chymotrypsin-like endopeptidase in the opossum kidney cell. 305 60

A proteinase from the venom of Vipera lebetina was purified by chromatography on Sephadex G-100 and CM-cellulose. The purified proteinase was homogeneous on SDS-polyacrylamide gel electrophoresis and consisted of a single chain with molecular weight of 37,000 +/- 1500. The isoelectric point of the proteinase was over 10. The enzyme was active on casein but not on esters and amides of arginine. It split the oxidized insulin B-chain at the peptide bonds of Tyr16-Leu17, Phe24-Phe25 and Phe25-Tyr26, and glucagon at the bonds Tyr10-Ser11, Leu14-Asp15 and Leu26-Met27. The enzyme was inhibited by DFP and PMSF, and partially by soybean trypsin inhibitor, but not with EDTA.
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PMID:Purification and properties of a proteinase from Vipera lebetina (snake) venom. 330 28

Oral administration to mice with soybean trypsin inhibitor (SBTI) (27-30 mg/mouse/day) or aprotinin (5500-6000 KIU/mouse/day) for six weeks increased the total pancreatic insulin (IRI). The pancreatic IRI was also increased after sc injections of synthetic caerulein (0.05 microgram/mouse/day divided into 3 daily doses), being 82% above the control levels when expressed per g pancreas. Aprotinin (6000 KIU/mouse/day divided into 3 daily doses) injected sc had no effect on the insulin content. The total glucagon did not change significantly in any of the groups, but the molar ratio of insulin to glucagon was increased in the caerulein- and SBTI-treated mice. Caerulein-treatment led to an increased disappearance rate of glucose with k-values being 7.1 +/- 0.3 compared to 6.0 +/- 0.1 (mean +/- SEM) in the controls (P less than 0.02). In islets isolated by collagenase-digestion of the pancreas and subjected to an overnight incubation, the content of insulin and glucagon was increased in islets from caerulein-treated animals. This corresponded to the results observed in the whole pancreas. The present study suggests that oral administration of proteolytic enzyme inhibitors or treatment with caerulein has a trophic effect on the endocrine pancreas. A difference in specificity seems to exist as SBTI affected both the pancreatic weight and IRI, and aprotinin orally did not influence the pancreatic weight, but increased the total content of IRI. Caerulein led to an increase in IRI, but did not affect the weight of pancreas.
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PMID:Effects of caerulein and trypsin inhibitors on the endocrine mouse pancreas. 616 52


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