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)

In this report we describe a novel in vitro phenomenon involving the interaction of insulin with purified protein phosphatases. Evidence is presented that porcine insulin is capable of activating and binding to rabbit skeletal muscle protein phosphatases in vitro. Its effects were examined on four rabbit skeletal muscle protein phosphatases. Two of these, phosphatases C-I and C-II, are of Mr approximately 35,000 and are the dissociated forms of protein phosphatase. The two other phosphatases, H-I and H-II, have Mr approximately 250,000 by gel filtration and represent nondissociated forms of phosphatase. Insulin reproducibly activated homogeneous preparations of protein phosphatase C-II and H-II approximately 3-5-fold in vitro. The activation was dependent on temperature, time, and insulin concentration. The activities of the phosphatases toward both phosphorylase alpha and histone were affected, indicating that this was not a substrate-directed effect. The activation phenomenon was not mimicked by insulin A or B chains, somatostatin, glucagon, or bovine serum albumin, and could be prevented by insulin antiserum. 125I-Insulin was shown to bind to the protein phosphatases by solid phase binding assays. Phosphatases C-I, C-II, and H-II, but not phosphatase H-I, were found to bind insulin reversibly. Half-maximal binding to the protein phosphatases was observed at approximately 5 X 10(-10) M insulin. Labeled insulin was found to coelute with protein phosphatase H-II on gel filtration when a mixture of the two was chromatographed, providing evidence for the formation of an enzyme-insulin complex. These findings suggest that certain protein phosphatases may have a specific binding site(s) for insulin and that these insulin-phosphatase complexes may also exhibit enhanced catalytic activity.
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PMID:A novel in vitro interaction of insulin with rabbit skeletal muscle protein phosphatases. 632 53

The characteristic amino acid pattern observed in chronic liver failure with high aromatic and low branched chain amino acid levels is considered to be consequent to increased muscle protein catabolism. The main catabolic stimulus has been attributed to hyperglucagonemia and to a reduced insulin/glucagon molar ratio. Intravenous administration of a solution containing branched chain amino acids and glucose to patients with chronic liver cirrhosis rapidly normalizes the plasma amino acid pattern. This effect may result from either a change in the insulin/glucagon ratio, induced by glucose, or from the anticatabolic influence of branched chain amino acids on muscle protein turnover. To discriminate between these two possibilities, a crossover study was carried out to determine the effect of a 24-hour infusion of either glucose alone, or glucose plus branched chain amino acids, in seven patients with chronic liver failure. Blood glucose, insulin, glucagon, free fatty acids, and amino acid levels were determined. Branched chain amino acids were much more effective than glucose (p less than 0.01) in decreasing the levels of aromatic amino acids. Conversely, the insulin, glucagon, and free fatty acid levels with glucose alone were not altered with the addition of branched chain amino acids. These findings suggest an anticatabolic effect of branched chain amino acids on muscle protein turnover and suggest that factors other than insulin and glucagon may be responsible for the characteristic plasma amino acid pattern present in chronic liver failure.
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PMID:Effect of glucose and/or branched chain amino acid infusion on plasma amino acid imbalance in chronic liver failure. 679 15

The rates of muscle protein breakdown, as estimated by the urinary excretion of 3-methylhistidine, were assessed in 30 cirrhotics and 15 controls on a strictly controlled diet. 3-Methylhistidine excretion was increased in cirrhotics irrespective of the etiology of the disease, and correlated with basal glucagon levels and with the insulin/glucagon ratio. In nine cirrhotics and nine age- and sex-matched controls, similar correlations were found between 3-methylhistidine and the areas under 24-hr glucagon or insulin/glucagon curves. A larger amount of 3-methylhistidine was excreted during the nighttime than during the daytime, when glucagon secretion was suppressed and the insulin/glucagon ratio was increased. It is concluded that muscle protein catabolism is increased in cirrhotics, possibly as a result of hyperglucagonemia or the reduced insulin/glucagon ratio. These data agree with the clinical observation of a progressive reduction in lean body mass which becomes evident in an advanced stage of the disease.
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PMID:Muscle protein breakdown in liver cirrhosis and the role of altered carbohydrate metabolism. 702 4

We have previously shown that spontaneous physical exercise can delay onset of experimental anorexia and cachexia, and retard tumour growth; we now report the effects on insulin sensitivity, hormonal levels and skeletal muscle protein metabolism. Insulin sensitivity determined with a euglycaemic hyperinsulinaemic clamp revealed a normalised glucose disposal rate in tumour-bearing exercising (TBE) versus sedentary (TBS) animals (TBE 15.55 +/- 2.71 versus TBS 2.47 +/- 2.12 mg/kg/min; P < 0.05). Both TBE and TBS animals had decreased levels of corticosterone during the clamp. Serum levels of insulin during tumour progression were unaffected by exercise, but the insulin: glucagon ratio increased and the progressive decrease in rT3 was attenuated. The concentration of glucagon decreased in both tumour-bearing groups during the experiment, while TBE animals showed a relative reduction in corticosterone. Capacity for skeletal muscle protein synthesis, expressed as RNA: protein ratio, was normalised in TBE animals in two tumour protocols (TBE 5.9 +/- 0.6 versus TBS 4.7 +/- 0.3; TBE 2.9 +/- 0.4 versus TBS 1.8 +/- 0.2; P < 0.05, respectively). Incorporation rate of 14C-phenylalanine into skeletal muscle protein was increased in the TBE group in vitro and in vivo. In the postexercise period, protein degradation evaluated by tyrosine release in vitro was increased, but decreased over time. This study has confirmed a positive skeletal muscle protein balance in exercising tumour-bearing animals, partly explained by the increased insulin sensitivity. This conclusion was further supported by the less catabolic pattern indicated by hormonal levels.
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PMID:Insulin sensitivity, hormonal levels and skeletal muscle protein metabolism in tumour-bearing exercising rats. 753 77

To study the immediate effects of stress hormones and intravenous amino acid support, healthy male volunteers were administered a stress-hormone infusion including epinephrine, cortisol, and glucagon either alone (Triple, n = 8) or combined with a balanced glutamine-free amino acid solution (Triple AA, n = 8) over a period of 6 hours. The amino acid infusion was started 2 hours after the hormone infusion. A third group (AA, n = 8) received the balanced amino acid solution alone. After 6 hours of the stress-hormone infusion, a decrease was observed in skeletal muscle protein synthesis as measured by the size distribution and concentration of ribosomes. The decrease was prevented by an infusion of the balanced amino acid solution. Following the triple-hormone infusion, a decrease was noted in the content of the total free amino acids in both muscle and plasma. After including amino acids in the infusion solution, the significant decrease in muscle glutamine caused by the triple hormones was not seen. Plasma cortisol, insulin, and glucose increased in response to the triple-hormone infusion alone or in combination with amino acids. In summary, the results show that the signs of muscle protein catabolism elicited by administration of stress hormones can be attenuated by simultaneous administration of a conventional amino acid solution, although it does not contain glutamine.
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PMID:Stress hormone and amino acid infusion in healthy volunteers: short-term effects on protein synthesis and amino acid metabolism in skeletal muscle. 808 90

The anabolic actions of GH are well known, although specific tissue responses and the mechanism of nitrogen conservation are less well understood. This study was designed to examine the acute metabolic effects of GH on whole body and regional protein metabolism, using an experimental protocol which controlled for confounding perturbations in other hormones by a simultaneous infusion of somatostatin. Control subjects received replacement doses of insulin, glucagon, and GH for the entire 7-h study period, whereas GH subjects received an identical protocol, except for an increased dose of GH sufficient to increase serum concentrations into the high-physiological range (12-20 ng/mL) for the final 3.5 h of the study (P < 0.001). Thirteen young, healthy male subjects were studied in the postabsorptive period; five served as control subjects and eight as treatment (GH) subjects. Each received continuous iv infusions of somatostatin, L-[13-C]leucine, and L-[2H5]phenylalanine throughout the study. Femoral arterial and venous sampling allowed for simultaneous measurements across the leg and in the whole body. C-Peptide levels were suppressed throughout the infusion; insulin, glucagon, insulin-like growth factor I, cortisol, epinephrine, norepinephrine, and glucose concentrations were not different between groups. Glycerol concentrations increased 3-fold in GH subjects during the final 3.5-h period (P = 0.04). Concentrations of several amino acids declined through the study, but no differences were observed between treatment groups. Leucine oxidation was reduced in GH compared to control subjects (P = 0.04). No changes in CO2 production or whole body leucine or phenylalanine flux were observed, whereas nonoxidative disposal of leucine was marginally higher in GH compared to control subjects (P = 0.07). By contrast, rates of appearance and disappearance of both leucine and phenylalanine across the leg all were relatively lower in GH compared to control subjects; leucine balance across the leg was reduced by GH (P = 0.03), whereas phenylalanine balance was not influenced by GH. Our data thus demonstrate an acute stimulatory effect of GH on lipolysis, a decrease in leucine oxidation, and no stimulation of muscle protein synthesis in spite of enhanced protein synthesis in nonmuscle tissue.
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PMID:Acute growth hormone effects on amino acid and lipid metabolism. 817 57

After 5 weeks of lactation 14 standard-fed primiparous sows were divided into a low weight-loss group (L-gr, loss < 25 kg, n = 7) and a high weight-loss group (H-gr, loss > or = 25 kg, n = 7). Body weights of the sows and their litters were recorded on days 2, 7, 14, 21, 28 and 35 of lactation. Blood samples were collected before the morning feeding on each weighing day. Samples were analysed to determine concentrations of insulin, glucagon, glucose, triglycerides, non-esterified fatty acids (NEFA), urea and creatinine. The H-gr sows lost weight throughout lactation, whereas the L-gr sows gained weight during the last week. Weight loss was higher in the H-gr than in the L-gr during weeks 2, 3 and 5 of lactation. Litter size and litter weight gain were higher in the H-gr than in the L-gr. Significant changes in levels of insulin, glucagon, glucose, triglycerides and creatinine were observed over lactation. No significant differences in concentrations of any of the parameters were found between the two groups, except for insulin and cholesterol which were higher in the L-gr. Catabolism of adipose tissue and muscle protein was observed in both groups during the first week of lactation. This catabolic state was more pronounced and tended to be prolonged in the H-gr. Concentrations of all parameters seemed to be stable in both groups during the last two weeks of lactation.
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PMID:Body weight loss during lactation in relation to energy and protein metabolism in standard-fed primiparous sows. 834 56

The purpose of this study was to examine the relationship of peripheral metabolism of glucose, lactate, alanine, and muscle protein catabolism to pyruvate availability during stress. Peripheral catabolic stress was simulated by the infusion of epinephrine, cortisol, and glucagon into the femoral artery of 12 healthy volunteers, 6 of whom received prior treatment with dichloroacetate while 6 served as controls. The catabolic hormone infusion reproduced the peripheral stress response in which glucose consumption increased and the efflux of lactate, alanine, and total amino acid nitrogen (i.e., net muscle protein catabolism) from the leg increased. Dichloroacetate (DCA), which is known to increase pyruvate oxidation, reduced the hormonally stimulated efflux of pyruvate and alanine from the leg and decreased the rate of extremity glucose consumption. DCA had no effect on the rate of lactate efflux and except for alanine had no effect on the stimulated rate of total amino acid nitrogen loss. These results demonstrate the dependence of alanine efflux on pyruvate availability during stress and suggest that the rate of glycolysis within peripheral tissues is a major factor in regulating the quantity of alanine efflux. This study further illustrates that except for alanine, pyruvate kinetics are not salient in the regulation of muscle protein catabolism and elucidates the dichotomy between alanine kinetics and true muscle protein breakdown.
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PMID:Dichloroacetate inhibits peripheral efflux of pyruvate and alanine during hormonally simulated catabolic stress. 841 69

The optimal nutritional support of critically ill patients should be based on the metabolic response. Therefore, we performed a series of experiments in patients using stable isotopic tracers designed to elucidate the responses of glucose, fatty acids, and protein metabolism in severely burned patients. Glucose production was elevated above normal as a result of an increase in glucagon concentration. The peripheral hypoglycemic action of insulin was diminished, as was its effectiveness in suppressing endogenous glucose production, but the intracellular capacity to oxidize glucose was not impaired. Lipolysis was stimulated by beta 2-adrenergic stimulation to a much greater extent than was fatty acid oxidation, with the result being an increase in the recycling of fatty acids secreted in very-low-density lipoproteins. Muscle protein catabolism was accelerated in severely burned patients, leading to a progressive loss of lean body mass that was not prevented by nutritional support alone. The ineffectiveness of nutritional support for muscle was due to alterations in amino acid transmembrane transport kinetics that favored efflux. Treatment with exogenous insulin stimulated inward amino acid transport and muscle protein synthesis. Extrapolation from our current knowledge of metabolism to clinical treatment indicates that nonprotein energy should be provided largely in the form of carbohydrate. If hyperglycemia ensues, exogenous insulin will further increase the anabolic response in muscle. Protein requirements can be met with 1.5 g protein.kg-1.d-1. Treatment with anabolic hormones may ultimately be the most effective way in which to optimize the response to nutritional support.
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PMID:Herman Award Lecture, 1996: relation of metabolic studies to clinical nutrition--the example of burn injury. 890 6

An anabolic stimulus is needed in addition to conventional nutritional support in the catabolic "flow" phase of severe trauma. One promising therapy appears to be rhGH infusion which has direct as well as hormonal mediated substrate effects. We investigated on a whole-body level, the basic metabolic effects of trauma within 48-60 h after injury in 20 severely injured (injury severity score [ISS] = 31 +/- 2), highly catabolic (N loss = 19 +/- 2 g/d), hypermetabolic (resting energy expenditure [REE] = 141 +/- 5% basal energy expenditure [BEE]), adult (age 46 +/- 5 y) multiple-trauma victims, before starting nutrition therapy and its modification after 1 wk of rhGH supplementation with TPN (1.1 x REE calories, 250 mg N.kg-1.d-1). Group H (n = 10) randomly received at 8:00 a.m. on a daily basis rhGH (0.15 mg.kg-1.d-1) and Group C (n = 10) received the vehicle of infusion. Protein metabolism (turnover, synthesis and breakdown rates, and N balance); glucose kinetics (production, oxidation, and recycling); lipid metabolism, (lipolysis and fat oxidation rates), daily metabolic and fuel substrate oxidation rate (indirect calorimetry); and plasma levels of hormones, substrates, and amino acids were quantified. In group H compared to group C: N balance is less negative (-41 +/- 18 vs -121 +/- 19 mg N.kg-1.d-1, P = 0.001); whole body protein synthesis rate is 28 +/- 2% (P = 0.05) higher; protein synthesis efficiency is higher (62 +/- 2% vs 48 +/- 3%, P = 0.010); plasma glucose level is significantly elevated (256 +/- 25 vs 202 +/- 17 mg/dL, P = 0.05) without affecting hepatic glucose output (1.51 +/- 0.20 vs 1.56 +/- 0.6 mg N.kg-1.min-1), glucose oxidation and recycling rates; significantly enhanced rate of lipolysis (P = 0.006) and free fatty acid reesterification (P = 0.05); significantly elevated plasma levels of anabolic GH, IGF-1, IGFBP-3, and insulin; trauma induced counter-regulatory hormone (cortisol, glucagon, catecholamines) levels are not altered; trauma induced hypoaminoacidemia is normalized (P < 0.05) and 3-methylhistidine excretion is significantly low (P < 0.001). Improved plasma IGF-1 levels in Group H compared with Group C account for protein anabolic effects of adjuvant rhGH and may be helpful in promoting tissue repair and early recovery. Skeletal muscle protein is spared by rhGH resulting in the stimulation of visceral protein breakdown. The hyperglycemic, hyperinsulinemia observed during rhGH supplementation may be due to defective nonoxidative glucose disposal, as well as inhibition of glucose transport activity into tissue cells. The simultaneous operation of increased lipolytic and reesterification processes may allow the adipocyte to respond rapidly to changes in peripheral metabolic fuel requirements during injury. This integral approach helps us to better understand the mechanism of the metabolic effects of rhGH.
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PMID:Integrated nutritional, hormonal, and metabolic effects of recombinant human growth hormone (rhGH) supplementation in trauma patients. 897 4


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