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 isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs-Ringer bicarbonate buffer containing 3 per cent bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, alpah1-acid glycoprotein, alpha2-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 mug.) used was insufficient to induce synthesis of alpha2-acute phase globulin, net syntheses of albumin, fibrogen, alpha1-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and alpha1-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.
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PMID:Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins. 6 Nov 40

The binding of labeled insulin to dissociated R3230AC mammary adenocarcinoma cells from diabetic and intact rats was investigated in vitro. At 20 degrees, specific binding (total binding minus binding in the presence of 1000-fold excess or 10(-6) M unlabeled insulin) reached a plateau at 45 to 60 min and was directly related to the number of cells used. Degradation of labeled insulin, as measured by trichloroacetic acid precipitation, was related to the number of cells used, was not prevented by trasylol or phenylmethylsulfonyl fluoride (general proteolytic enzyme inhibitors), but was prevented by addition of 1 to 2% bovine serum albumin to the incubation medium. Specificity of insulisulin, and desoctapeptide insulin were capable of competing for insulin binding in an order of potency related to their relative biological activity; prolactin and glucagon were unable to compete for insulin binding. Scatchard analysis of the binding data demonstrated a curvilinear-plot; specific binding (over the concentration range of 10(-11) to 10(-10) M insulin) showed a high affinity (Kd approximately 1 to 3 X 10(-10) M), and the estimated number of sites was greater in tumors from diabetic animals than in tumors from intact animals or intact animals given insulin prior to sacrifice. Reversibility of insulin binding was studied by dissociation experiments; dissociation was enhanced in the presence of added unlabeled insulin compared to dissociation examined under conditions of "infinite" dilutions only. Maximum dissociation of bound insulin was observed in the presence of 10(-7) M unlabeled insulin, with less of an effect at lower or higher concentrations of added insulin (no effect seen at 10(-10) M insulin). Two techniques were investigated for separating cells from unbound labeled insulin; the procedure using centrifugation was found to be more efficient. Thus, in the R3230AC mammary adenocarcinoma, data obtained on saturability, reversibility, and specificity of insulin binding indicate the existence of an insulin receptor with properties similar to those found in normal cells.
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PMID:Identification and characterization of the insulin receptor in the R3230AC mammary adenocarcinoma of the rat. 13 40

The beige mouse, C57BL/6 (bg/bg), is an animal model for the Chediak-Higashi syndrome in man, a disease characterized morphologically by giant lysosomes in most cell types. Half-lives for the turnover of [(14)C]bicarbonate-labeled total soluble liver protein were determined in normal and beige mice. No significant differences were observed between the normal and mutant strain for both rapidly and slowly turning-over classes of proteins. Glucagon treatment during the time-course of protein degradation had similar effects on both normal and mutant strains and led to the conclusion that the rate of turnover of endogenous intracellular protein in the beige mouse liver does not differ from normal. The rates of uptake and degradation of an exogenous protein were determined in normal and beige mice by intravenously injecting (125)I-bovine serum albumin and following, in peripheral blood, the loss with time of phosphotungstic acid-insoluble bovine serum albumin and the parallel appearance of phosphotungstic acid-soluble (degraded) material. No significant differences were observed between beige and normal mice in the uptake by liver lysosomes of (125)I-bovine serum albumin (t((1/2)) = 3.9 and 2.8 h, respectively). However, it was found that lysosomes from livers of beige mice released phosphotungstic acid-soluble radioactivity at a rate significantly slower than normal (t((1/2)) = 6.8 and 3.1 h, respectively). This defect in beige mice could be corrected by chronic administration of carbamyl choline (t((1/2)) = 3.5 h), a cholinergic agonist which raises intracellular cyclic GMP levels. However, no significant differences between normal and beige mice were observed either in the ability of soluble extracts of liver and kidney to bind [(3)H]cyclic GMP in vitro or in the basal levels of cyclic AMP in both tissues. The relevance of these observations to the presumed biochemical defect underlying the Chediak-Higashi syndrome is discussed.
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PMID:Protein degradation in normal and beige (Chediak-Higashi) mice,. 20 11

1. Heat output by suspensions of isolated rat hepatocytes was determined by using a modified batch-type microcalorimeter. 2. The ratio of O(2) uptake (determined polarographically) to heat output was used to assess the metabolic efficiency of isolated hepatocytes. 3. Cells from starved or fed rats incubated in either bicarbonate-buffered physiological saline containing gelatin, or bicarbonate-buffered physiological saline containing amino acids, serum albumin and glucose showed no significant difference with respect to the ratio of O(2) uptake to heat output. 4. For liver cells from 24h-starved rats, the addition of 10mm-dihydroxyacetone and 2.5mm-fructose significantly decreased the ratio of O(2) uptake to heat output from 1.94+/-0.05 in the controls to 1.52+/-0.04 and 1.54+/-0.01mumol/J respectively. 5. Glucagon (1mum), which slightly increased both O(2) uptake and heat output, did not significantly alter the ratio. 6. The addition of extracellular 10mm-NH(4)Cl and urease to provide an energetically wasteful cycle by ensuring hydrolysis of newly synthesized urea, lowered the ratio of O(2) uptake to heat output from 1.81+/-0.08 to 1.47+/-0.06mumol/J, indicating a reduced metabolic efficiency. 7. Metabolic efficiency in rats of different dietary regimen, age and genetically based obesity was also assessed. No differences in the ratio of O(2) uptake to heat output were found between liver cell suspensions prepared from rats maintained on colony diet and high-fat diet or sucrose-rich diet nor between animals ranging from 38 to 179 days of age. Comparison of the ratio of liver cell O(2) uptake to heat output between homozygote Zucker fa/fa obese rats and their lean littermates showed no significant difference. 8. It is concluded that the ratio of O(2) uptake to heat output for isolated hepatocytes is relatively constant unless perturbed by conditions that markedly enhance substrate cycling.
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PMID:The application of microcalorimetry to the assessment of metabolic efficiency in isolated rat hepatocytes. 48 37

Seven rabbits were immunized with a synthetic C-terminal glucagon fragment [15--29] conjugated with bovine serum albumin by means of glutaraldehyde. Antisera for glucagon were produced in all the animals after six injections of the conjugate. One of them revealed a higher titer antiserum (G42), which did not cross react with gut glucagon-like immunoreactive material, secretin, insulin, gastric inhibitory polypeptide or vasoactive intestinal peptide. From the results of inhibition of 125 I-glucagon in binding with the antiserum by various glucagon-related fragments the immunogenic determinant of the antiserum was proved to be in the C-terminal residue of the glucagon molecule, although peptide [17--29] or [21--29] reacted weakly with the antiserum. The plasma glucagon levels measured by antiserum G 42 during an arginine test in five normal subjects were superposed on those obtained by other antiserum (G21), specific for pancreatic glucagon. Furthermore, a comparable standard curve for glucagon was obtained using antiserum G42, when a labelled p-hydroxyphenylacetylated glucagon fragment [15--29] was employed as a tracer. The present study clearly demonstrated that the C-terminal glucagon fragment could yield a specific antiserum for pancreatic glucagon, supporting the proposal that the C-terminal fragment of glucagon is responsible for such specific antisera. Furthermore, it is concluded that immunoassay for glucagon could be performed using the labelled glucagon fragment as a tracer.
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PMID:Production of a specific antiserum by synthetic C-terminal fragment of glucagon. 57 20

For the study of insulin and glucagon secretion at the isolated perfused rat pancreas are used, as a rule, synthetic perfusion media that have to meet two requirements: They have to ensure the biological function of the perfused organ for 2 hrs, and must not interfere with radioimmunological insulin and glucagon determination. An appropriate medium is the Krebs-Ringer bicarbonate buffer at pH 7.4 with addition of 4% dextran (MG 75000) and 0.5% human serum albumin; it allows one to produce, after permanent glucose stimulation, a biphasic insulin secretion. Infusion media based on gelatine or polyvinylpyrrolidone proved inadequate for these studies.
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PMID:[Insulin and glucagon secretion in the isolated perfused rat pancreas]. 97 49

The exchange of 125I-insulin, 125I-glucagon, 125I-proinsulin, 125I-growth hormone, 131I-albumin, 14C-inulin, and 14C-dextran across isolated rat mesentery was studied in a diffusion cell. The passage of immunoprecipitable porcine 125I-insulin (0.88 ng./ml.) was not affected by porcine proinsulin (145 ng./ml.), crystalline porcine insulin (17.4 ng./ml.), human growth hormone (87 ng./ml.), bovine serum albumin (4.5 mg./ml.), or normal guinea pig serum (840 mug. protein/ml.). However, the rate of insulin exchange was reduced by guinea pig anti-insulin antiserum and partially purified human serum-bound insulin (175 mug. protein/ml.). Bound insulin at the same concentration did not affect the exchange of 125I-glucagon, 125I-growth hormone, 14C-inulin, or 14C-dextran. Further purification of bound insulin by Sephadex G-100 chromatography yielded an approximately 45,000-molecular-weight fraction that at 5 mug. protein permilliliter allowed essentially no insulin transport. This same fraction of bound insulin significantly inhibited the disappearance of immunoprecipitable porcine 125I-insulin from the incubation medium of isolated rat hemidiaphragms. Theses studies suggest that the transport of insulin across biologic membranes, mesothelium, and possible endothelium is specifically inhibited by bound insulin, a circulating macromolecule that possesses insulin-like activity.
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PMID:Transport of peptide hormones across isolated rat mesentery: effect of human serum-bound insulin. 118 35

This study used 10-nm gold particles with 5-7 insulin molecules attached (Au10-Ins) to investigate the site of interaction of insulin with the nuclear envelope during insulin uptake into intact isolated nuclei. Despite its size, and in the absence of ATP, Au10-Ins entered nuclei through the nuclear pore and associated with the heterochromatin. Because Au10-Ins is essentially gold-bovine serum albumin (Au-BSA) with a few insulin molecules attached, the effect of insulin and other growth factors on the nuclear accumulation of BSA coupled to 10-, 15-, and 24-nm-diam colloidal gold particles (Au10-BSA, Au15-BSA, and Au24-BSA) was determined. The Au-BSA complexes were excluded from nuclei in the absence of insulin. Insulin (0.5-100 ng/ml) caused a dose-dependent accumulation of Au10-BSA in the nucleus. The nuclear membrane was shown to be intact by several criteria, therefore, accumulation of Au-BSA occurred via the nuclear pore and was not due to leakage across or through the membrane. Uptake of 15- and 24-nm Au-BSA molecules was not affected by insulin, suggesting the hormone had a limited effect in increasing the functional diameter of the nuclear pores. Glucagon, epidermal growth factor, platelet-derived growth factor, insulinlike growth factor I, and insulin A or B chains did not stimulate the accumulation of Au10-BSA. The insulin-stimulated accumulation of Au10-BSA was blocked by concanavalin A, mimicked by wheat-germ agglutinin, and did not require ATP. The Au10-BSA in the nucleus was associated with heterochromatin, suggesting it bound to a nuclear element.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin stimulates accumulation and efflux of macromolecules in isolated nuclei from H35 hepatoma cells. 173 9

A procedure for maintaining broiler adipocytes in culture was established and used to evaluate the effect of selected culture ingredients on glucagon-stimulated lipolysis. Adipocytes were isolated by collagenase and trypsin digestion of abdominal adipose tissue from 40- to 70-day-old broilers. Freshly isolated adipocytes did not exhibit glucagon-stimulated lipolysis. However, after 24 h in culture, lipolysis was stimulated maximally at doses of glucagon from 5 to 100 ng/mL with 50% stimulation occurring at .7 +/- .4 ng/mL. This responsiveness was maintained for an additional 24 h in culture. Inclusion of 2 or 5% chicken serum in the medium reduced (P less than or equal to .05) the responsiveness of the cells to glucagon. A 30% reduction (P less than or equal to .001) in responsiveness occurred when bovine serum albumin was removed from the medium. The results indicate that broiler adipocytes can be maintained in culture and that certain culture ingredients alter the responsiveness of the cells to glucagon.
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PMID:Glucagon-stimulated lipolysis of primary cultured broiler adipocytes. 202 37

Comparatively low level of serum insulin and tissue insulin resistance are characteristic of the stage of burn hypermetabolism. In order to evaluate the effect of tolbutamide in reducing burn hypermetabolism rate, 18 adult male rabbits weighing 1.8-2.5 Kg were subjected to 30% TBSA full thickness burns and randomized into treated and control groups. In the treated group, tolbutamide (90mg/Kg/day) was introduced into the stomach from 4 hours to 10 days postburn. Animals of both group were fed with specified food (protein 15%, glucose 80%) after burn. The values of serum glucose, insulin, glucagon, oxygen expenditure and other nutritional indices were measured before burn and 1, 3, 6, 10 days postburn. Their changes were as follows: (1) Serum glucose levels of the treated group were obviously lower than those of the control group (P less than 0.01). (2) Serum insulin levels and the ratio of I/G (insulin/glucagon) of the treated group were significantly higher than those of the control group (P less than 0.01). (3) The indices of cumulative N balance, oxygen expenditure, serum albumin in the treated group were better than that in the control (P less than 0.05-0.001). It is concluded that tolbutamide can reduce burn hypermetabolism probably through the following ways: 1. stimulation of the secretion of insulin and enhancement of the effect of insulin; 2. inhibition of the secretion of glucagon; 3. improvement in tissue insulin resistance and promotion of glucose utilization of skeletal muscles.
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PMID:[Tolbutamide and burn hypermetabolism]. 203 79


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