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)

Factitious hyperinsulinism was suspected in a patient with an 11-year history of insulin-dependent, ketosis-prone diabetes mellitus who began to experience repetitive episodes of "spontaneous" hypoglycemia. Insulin mediation of the hypoglycemia was confirmed by documenting that urinary insulin and total extractable insulin in plasma increased during periods of hypoglycemia. Failure to detect significant amounts of human C-peptide by radioimmunoassay during periods of hypoglycemia or in response to stimulation with glucagon, leucine, or tolbutamide indicated that the insulin was not endogenous. The diagnosis of factitious hyperinsulinism was ultimately proved by the finding of radioactivity in the patient's urine after 131-I Hippuran was added to a vial of insulin found in the patient's room.
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PMID:Plasma C-peptide and diagnosis of factitious hyperinsulinism. Study of an insulin-dependent diabetic patient with "spontaneous" hypoglycemia. 111 42

Trypsin and elastase isolated from the pancreas of the moose (Alces alces), a member of the Cervidae (deer) family, were characterized with respect to their amino acid composition and specificity towards polypeptides. Moose trypsin possessed 234 residues, based on alanine recoveries equal to 16.0 residues, with a molecular weight calculated at 24 476. Moose trypsin readily hydrolysed peptide bonds in which the carbonyl group was contributed by arginine, lysine and S-2-aminoethylcysteine as indicated by the peptides isolated following hydrolysis of the oxidized and the S-aminoethylated B-chain of insulin. Moose elastase possessed 231 residues, based on alanine recoveries equal to 17.0 residues, with a molecular weight calculated as 24 201. The high lysine (9 residues), low arginine (3 residues) content was in contrast to the opposite situation with porcine elastase and the elastase-like, alpha-lytic protease from Sorangium. The hydrolysis of the oxidized B-chain of insulin by moose elastase was similar to that produced by porcine elastase with major cleavages occurring at Val-12-Glu-13, Ala-14-Leu-15 and Val-18-Cys(O-3H)-19 and minor cleavages occurring at Ser-9-His-10 and Arg-21-Gly-22. The hydrolysis of glucagon with moose elastase produced major cleavages at Thr-7-Ser-8, Ser-11-Lys-12, Val-23-Gln-24 and Leu-26-Met-27. The facile hydrolysis of Arg-17-Arg-18 was also observed and attributed, in part, to trypsin.
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PMID:Characterization of trypsin and elastase from the moose (Alces alces). I. Amino acid composition and specificity towards polypeptides. 112 77

Six normal subjects received 10 g of alanine both orally and as a 60-min intravenous infusion. In both studies blood samples for hormones and substrates were obtained every thirty minutes for 2 1/2 hour. Significant increases in whole blood levels of threonine, serine, glutamine, proline, glycine, and alpha-amino-n-butyric acid were found, which were mainly due to increases of these amino acids in the plasma compartment. In contrast, whole blood levels of leucine, valine, and isoleucine declined, mainly due to increases in the cell compartment. Plasma glucagon levels increased in both studies while insulin levels rose significantly only during the oral study. Plasma free fatty acids and blood glycerol levels declined while lactate and pyruvate increased. Glucose concentration did not change during both tests. These data suggest that the administration of large quantities of alanine is capable of inducing significant alterations in levels of other amino acids and substrates as well as changing hormone levels.
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PMID:Alanine-induced amino acid interrelationships. 116 33

The net hepatic metabolism of amino glycerol, lactate, and pyruvate was determined in conscious fed sheep by multiplying the venoarterial concentration differences by the hepatic blood or plasma flow. In each experiment several sets of control blood samples were taken; glucagon or insulin then was infused intraportally for 2 h during which additional samples were taken. Four types of experiments were performed: 1) glucagon infusion (150 mug/h) into normal sheep, 2) glucagon infusion (100 mug/h) into insulin-treated alloxanized sheep, 3) insulin infusion (1.17 U/h) into normal sheep, and 4) insulin plus glucose infusion (12.3 mmol/h) into normal sheep. The second group of experiments was performed to prevent reflex hyperinsulinemia, and the fourth was performed to prevent reflex hyperglucagonemia. Glucagon directly stimulated the net hepatic uptake of alanine, glycine, glutamine, arginine, asparagine, threonine, serine, and lactate. Glucagon also stimulated lipolysis in adipose tissue. Insulin, on the other hand, appeared to have a lipogenic effect on adipose tissue and to stimulate directly the uptake of valine, isoleucine, leucine, tyrosine, lysine, and alanine only at extrahepatic sites. The study showed that, in sheep, the effects of glucagon primarily are on liver, and insulin's effects primarily are on skeletal muscle and adipose tissue where it promotes protein and lipid synthesis.
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PMID:Effects of glucagon and insulin on net hepatic metabolism of glucose precursors in sheep. 120 Jan 53

The catabolism of glucose and amino acids has been studied in the normal, the fasted, and the fasted septic dog. The fasted septic dog oxidized more glucose and alanine, and had more gluconeogenesis from alanine and the five tritiated amino acids--glutamate, threonine, phenylalanine, leucine, and valine--as compared to the normal and equally fasted dog. Thus the total body protein catabolic state was characterized in biochemical terms. In contrast, following glucose infusion, the fasted septic animal responded much like the fasted animal in terms of decreased animo acid gluconeogenesis and decreased plasma concentrations of amino acids, fats and fat products, but considerably increased the oxidation of alanine. The increased alanine oxidation appeared to be primarily related to increased tissue clearance and increased plasma concentration. There was some suggestive evidence for enhanced oxidation of the tritiated amino acids including leucine and valine during glucose infusion. The protein catabolic state secondary to this sort of sepsis in dogs only on per os fluid support appears to be best characterized as a glucose catabolic state with alanine being oxidized directly. Such states are known to be ones of enhanced metabolic rate secondary to enhanced synthetic processes generally. This is probably related to enhanced sympathetic nervous system release of glucagon with insulin being normally responsive to glucose because of a normal plasma epinephrine.
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PMID:Turnover of amino acids in sepsis and starvation: Effect of glucose infusion. 125 26

The goal of this investigation was to identify the metabolic abnormalities in a group of colon cancer patients before and during 5-fluorouracil chemotherapy. Twenty-two colon cancer patients were prospectively enrolled into a Clinical Research Center for measurement of counter regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA), and leucine oxidation (LO). Both the cancer group and the normal volunteers were matched for nutrition status (109 +/- 5% of ideal body weight vs 104 +/- 4%, mean +/- SEM, respectively) and history of weight loss (6.3 +/- 2.6 kg vs 4.4 +/- 4.8). Plasma growth hormone was significantly elevated in the colon cancer patients (3.22 +/- 0.62 ng/mL vs 0.73 +/- 0.18, p < .05) despite the fact that insulin-like growth factor-1 levels were not different. Plasma glucose, insulin, cortisol, glucagon, epinephrine, and norepinephrine levels were not significantly different than those of the normal volunteers. Fasting HGP rates were slightly but not significantly elevated in the group of colon cancer patients compared with the normal volunteers (2.09 +/- 0.11 mg/kg per minute vs 1.79 +/- 0.10, p = .10). Plasma LA was not significantly elevated in the colon cancer group (63.3 +/- 3.0 mumol/kg per hour vs 57.7 +/- 4.2; p = .25). Five days of continuous 5-fluorouracil chemotherapy was associated with a significant elevation in both the fasting glucose level (97 +/- 3 mg/dL vs 106 +/- 5, p < .05), and HGP (2.09 +/- 0.11 mg/kg per minute vs 2.27 +/- 0.10; p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic response to chemotherapy in colon cancer patients. 128 27

Northern-blot analysis was used to demonstrate that an increase in extracellular glucose concentration increased the content of preproinsulin mRNA 2.3-fold in the beta-cell line HIT T15. A probe for the constitutively expressed glyceraldehyde-3-phosphate dehydrogenase was used as a control. Mannoheptulose blocked this effect of glucose. A stimulatory effect on preproinsulin mRNA levels was also observed in response to mannose and to 4-methyl-2-oxopentanoate. However, galactose and arginine were ineffective. Glucagon, forskolin and dibutyryl cyclic AMP also elicited an increase in HIT-cell preproinsulin mRNA. The ability of the 5' upstream region of the preproinsulin gene to mediate the effect of glucose and other metabolites on transcription was studied by using a bacterial reporter gene technique. HIT cells were transfected with a plasmid, pOK1, containing the upstream region of the rat insulin-1 gene (-345 to +1) linked to chloramphenicol acetyltransferase (CAT). Co-transfection with a plasmid pRSV beta-gal containing beta-galactosidase driven by the Rous sarcoma virus promoter was used as a control for the efficiency of transfection; expression of CAT activity in transfected HIT cells was normalized by reference to expression of beta-galactosidase. Glucose caused a dose-dependent increase in expression of CAT activity, with a half-maximal effect at 5.5 mM and a maximum response of 4-fold. Mannoheptulose blocked this effect of glucose. Other metabolites (mannose, 4-methyl-2-oxopentanoate and leucine plus glutamine) were also able to increase insulin promoter-driven CAT expression, but galactose and arginine were ineffective. The stimulatory effect of glucose on CAT expression was not blocked by verapamil and was inhibited by increasing extracellular Ca2+ from 0.4 to 5 mM. Both dibutyryl cyclic AMP and forskolin caused an increase in insulin promoter-driven gene expression in the presence of 1 mM-glucose, but neither agent further increased the level of expression occurring in the presence of a maximally stimulating glucose concentration. The phorbol ester phorbol 12-myristate 13-acetate (PMA) also increased insulin promoter-driven CAT expression in the presence of 1 mM-, but not 11 mM-glucose. Staurosporine blocked the stimulatory effect not only of PMA but also of glucose and of dibutyryl cyclic AMP. We conclude that the 5' upstream region of the insulin gene contains sequences responsible for mediating the stimulatory effect of glucose on insulin-gene transcription.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Control of insulin gene expression by glucose. 132 37

Retinoblastoma protein (RB) is a tumor suppressor gene product involved in embryogenesis and cell cycle progression. One of the major mechanisms leading to RB dysfunction is complex formation with viral oncoproteins using the common RB binding motif Leu X Cys X Glu (LXCXE) which has also been identified in cellular ligands, e.g., RBP-1 and RBP-2. p107, a cellular protein with RB sequence homology, has been shown to bind to the same viral oncoproteins associating with RB and is therefore thought to contribute to cell cycle regulation. It has recently been suggested that insulin stimulates gene transcription through direct association with an, as yet, unidentified intracellular transcription factor. Due to the central roles of RB and p107 in coupling external growth signals with the progression of the cell cycle clock, we have hypothesized that these two proteins might be candidates for mediating the effects of insulin on DNA. We report here the identification of a region in the B-chain of human insulin that has the sequence LXCXE. Based on this finding we predict that the insulin B-chain may interact with RB and/or p107. Since we have also identified sequences hydropathically related to LXCXE in insulin-like growth factor I (IGF-I) and II (IGF-II), but not in relaxin, nerve growth factor, epidermal growth factor, glucagon or beta-endorphin, we further propose that both IGF-I and -II may assemble with RB and/or p107, too. Moreover, binding sites on RB and p107 identical with those suggested for viral oncoproteins and cellular ligands are predicted for insulin/IGF-I/IGF-II by using the hydropathic complementarity approach.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proposed interaction between insulin and retinoblastoma protein. 133 81

1. Isolated cat hepatocytes were established in monolayer culture, cell proteins labelled with tritiated leucine and the effects of amino acids and hormones on the regulation of intracellular protein breakdown were studied. 2. Mixtures of essential and non-essential amino acids inhibited the breakdown of long-lived protein, but when tested individually, amino acids except for tryptophan were ineffective. 3. The rate of breakdown of short-lived protein was not regulated by amino acids or hormones, a finding which was similar to that in rat liver cells. 4. The known stimulatory hormones of proteolysis in rat liver such as glucagon, dexamethasone and corticosteroids failed to enhance protein degradation in cat liver cells. 5. These results support the contention that the control of protein degradation in the cat is different to that in the rat and these differences may reflect the unusual protein metabolism of the cat.
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PMID:The control of protein degradation in monolayer cultures of cat hepatocytes. 139 92

Incorporation of L-[1-13C]leucine into muscle protein and leg exchange of L-[15N]phenylalanine were used to assess the effects over 240 min of amino acid supply on leg protein turnover in anesthetized, overnight-fasted (Landrace x Great White) female pigs. In all pigs, plasma insulin and glucagon stability was ensured by infusion of somatostatin (8 micrograms.kg-1.h-1), insulin (6 mU.kg-1.h-1), and glucagon (72 ng.kg-1.h-1). Mixed amino acid infusion (260 mg.kg-1.h-1) caused a 2- to 2.5-fold elevation of arterial plasma phenylalanine and leucine; in a control group (no amino acid infusion), an increase in phenylalanine and leucine concentration was observed as a result of the hormone clamp. Plasma insulin and glucagon concentrations were steady and not significantly different between control and amino acid-infused groups during the final 240 min, but plasma glucose fell (P less than 0.05) in both groups (4.57 +/- 0.17 to 3.15 +/- 0.73 mM). Muscle protein synthetic rate (estimated from the change in L-[1-13C]leucine incorporation compared with labeling of [13C]leucyl-tRNA) was greater in amino acid-infused (0.076%/h) than in control (0.053%/h) pigs. In the control group, leg amino acid balance was negative (Phe alone, -10.2 +/- 9.4 nmol Phe.100 g-1.min-1; total amino acids, -0.27 +/- 1.04 micrograms amino N.100 g-1.min-1), but during amino acid infusion, balance was positive (Phe alone, +33.6 +/- 8.8 nmol Phe.100 g-1.min-1; total amino acids, +58.2 +/- 4.9 micrograms amino N.100 g-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of protein synthesis in pig skeletal muscle by infusion of amino acids during constant insulin availability. 141 25


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