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 effect of metabolic acidosis (MA) on amino acid and keto acid metabolism was studied in fourteen patients with chronic renal failure (CRF) under the low protein diet (0.6-0.8 g/kgBW). The comparative study of five patients with renal tubular acidosis was carried out. Each patient was investigated before [MA(+)period] and after correction with sodium bicarbonate administration lasting 10 days [MA(-)period]. The correction of MA improved nitrogen balance and elevated plasma branched-chain amino acids (BCAA), keto acids (BCKA), glutamine and alanine concentrations. No effect was however, observed in change of plasma insulin and glucagon. Oral administration of the keto-analogues of BCKA [0.1 g/kgBW of alpha-ketoisovalerates (KIV) and alpha-keto-isocaproic acid (KIC)] is made for the purpose of investigating the change in the metabolic conversion rate to amino acids. As a result, MA (+) suppressed an increase in plasma KIV and KIC concentrations. Moreover, an increase in plasma valine and leucine concentrations were suppressed by MA (+). These results suggested that MA stimulates BCKA oxidation and suppresses the protein sparing effect of leucine and KIC, and accelerates the catabolism in CRF under the low protein diet. The correction of MA is ineffective in severe renal failure (serum creatinine above 10.0 mg/dl), because the other uremic factors appear to be affecting protein and amino acid metabolism. Therefore, it might be concluded that MA should be corrected at an earlier stage of CRF.
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PMID:[The effect of metabolic acidosis on amino acid and keto acid metabolism in chronic renal failure]. 205 49

The activity of phosphate-dependent glutaminase and glutamine metabolism by tissues known markedly to utilize or synthesize glutamine (or both) were studied in rats made septic by cecal ligation and puncture technique and compared with the same measures in rats that underwent sham operation (laparotomy). Blood glucose level was not markedly different in septic rats, but lactate, pyruvate, alanine, and glutamine levels were markedly increased. Conversely, blood ketone body concentrations were significantly decreased in septic rats. Both plasma insulin and glucagon levels were markedly elevated in response to sepsis. The maximal activity of phosphate-dependent glutaminase was decreased in the small intestine, increased in the kidney and mesenteric lymph nodes, and unchanged in the liver of septic rats. Arteriovenous concentration difference measurements across the gut showed a decrease in the net glutamine removed from the circulation in septic rats. Arteriovenous concentration difference measurements for glutamine showed that both renal uptake and skeletal muscle release of the amino acid were increased in response to sepsis, whereas measurements across the hepatic bed showed a net uptake of glutamine in septic rats. Enterocytes isolated from septic rats exhibited a decreased rate of utilization of glutamine and production of glutamate, alanine, and ammonia, whereas lymphocytes isolated from septic rats showed an enhanced rate of utilization of glutamine and production of glutamate, aspartate, and ammonia. It is concluded that, during sepsis, glutamine uptake and metabolism are enhanced in renal and lymphoid tissue but decreased in that of the small intestine, with increased rates of release by skeletal muscle; however, the liver appears to utilize glutamine in septic rats.
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PMID:Maximal activity of phosphate-dependent glutaminase and glutamine metabolism in septic rats. 206 39

Infusion of total parenteral nutrition (TPN) with excess carbohydrate calories leads to hepatic steatosis in rats and is associated with an elevated portal insulin/glucagon molar ratio. Previously we have shown that adding glucagon to TPN prevents and reverses hepatic steatosis in rats, possibly by increasing hepatic lipid export. It has been reported that steatosis is eliminated in rats by the addition of L-glutamine to TPN. In this study, we examined the effect of glutamine on portal insulin and glucagon levels and the development of hepatic steatosis. Adult rats (n = 19) received internal jugular catheters: Group 1 (n = 6), saline (3 cc/hr) and chow ad libitum; Group 2 (n = 7), 25% dextrose base TPN; Group 3 (n = 6), 25% dextrose base TPN with 2% glutamine. The infusion rate of TPN was 1.2 cc/100 g body wt/hr. Daily nitrogen balance was determined and at 7 days, portal venous blood was drawn for insulin and glucagon radioimmunoassay, livers were removed for histology and lipid content determination, and the small intestines were removed for mucosal protein and DNA content determination. Panlobular vacuolization of the hepatocytes was noted on histology in Group 2 (TPN) while Group 1 (chow) and Group 3 (TPN + glutamine) showed normal liver morphology. Hepatic lipid content was significantly elevated in Group 2 (P less than 0.05). The portal insulin/glucagon molar ratio was increased because of excessive portal venous insulin in Group 2 (TPN). In contrast, portal glucagon was significantly elevated while the insulin/glucagon ratio and hepatic lipid content did not increase above control levels in the glutamine-supplemented Group 3 rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Addition of L-glutamine to total parenteral nutrition and its effects on portal insulin and glucagon and the development of hepatic steatosis in rats. 211 67

The intestinal metabolism of glucose and glutamine was studied in rats made septic by cecal ligation and puncture technique. Sepsis resulted in negative nitrogen balance and produced increases in the concentrations of blood pyruvate, lactate, alanine, and glutamine, and decreases in those of 3-hydroxybutyrate and acetoacetate. Both plasma insulin and glucagon concentrations were increased by 2.2- and 3.2-fold in septic rats, respectively. Portal-drained visceral blood flow increased in septic rats, and was accompanied by a decrease in the rates of utilization of glutamine and production of lactate, glutamate, and ammonia compared with those rates in sham-operated animals. Enterocytes isolated from septic rats showed decreased rates of glucose and glutamine utilization compared with cells isolated from corresponding controls. The maximal activities of hexokinase, 6-phosphofructokinase, pyruvate kinase, and glutaminase were decreased in intestinal mucosal scrapings of septic rats. It is concluded that a moderate form of sepsis decreases the rates of glucose and glutamine utilization (both in vivo and in vitro) by the epithelial cells of the small intestine. This may be caused by changes in the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells as a metabolic adaptation to spare glucose and glutamine for use by other tissues.
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PMID:Glucose and glutamine metabolism in the small intestine of septic rats. 236 28

Glutamine is an important amino acid because of its key role in the transfer of both carbon and nitrogen between tissues in the body. Specific tissues are usually associated with either net synthesis or net utilization of glutamine, but the liver plays a central role in glutamine homeostasis, in that it can shift to function in either capacity. This capability, along with the localization of urea biosynthesis in the periportal hepatocytes, focuses attention on the transport mechanisms in hepatocytes for uptake and release of glutamine. Active transport of glutamine by hepatocytes is mediated by a Na(+)-dependent activity termed system N, which exhibits a rather narrow substrate specificity mediating uptake of histidine and asparagine as well as of glutamine. This secondary active transport system allows for the net accumulation of glutamine against a concentration gradient and maintenance of intracellular concentrations of glutamine between 4 and 8 mM in the face of a plasma concentration of 0.6 mM. Utilization of the Na+ electrochemical gradient as a driving force ensures that the system N carrier catalyzes a unidirectional transport event favoring the cytoplasm. It is obvious from the glutamine gradient across the plasma membrane that efflux of this amino acid is typically slower than accumulation; measurement of saturable, Na(+)-independent glutamine transport by system L substantiates this proposal. However, it is clear that under certain metabolic conditions the liver represents a source of glutamine for other tissues in the body and net efflux must occur. The system N transport activity in hepatocytes is regulated by hormones such as insulin, glucagon, and glucocorticoids, as demonstrated both in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristics and regulation of hepatic glutamine transport. 240 55

In the isolated perfused rat pancreas, D,L-difluoromethylornithine, tested at a concentration of 3 mmol/L, failed to affect the release of glucagon and insulin caused, over 15 min stimulation, by either L-arginine or L-ornithine (2.0, 5.0 or 10.0 mmol/L) in the presence of either 3.3 or 5.6 mmol/L D-glucose. The inhibition of ornithine decarboxylase also failed to affect the release of glucagon provoked by either L-leucine (2 or 3 mmol/L) or L-glutamine (2 mmol/L) and the secretion of insulin stimulated by a rise in glucose concentration from 5.6 to 10.6 mmol/L. These data are interpreted to suggest that the rapid generation of polyamines from either L-arginine or L-ornithine does not play any significant role in the immediate glucagonotropic and insulinotropic action of these cationic amino acids.
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PMID:Stimulus-secretion coupling of arginine-induced insulin release. Resistance of arginine- and ornithine-stimulated glucagon and insulin release to D,L-alpha-difluoromethylornithine. 240 45

The effect of amino acids, in concentrations corresponding to those found in the portal vein of rats given a high-protein diet, was investigated on the activity of system A amino acid transport in hepatocytes from fed rats. Amino acids counteracted the induction of system A by insulin or glucagon. This effect was observed at all concentrations of hormones tested, up to 1 microM. Amino acids did not affect the basal cyclic AMP concentration in hepatocytes, or the large rise in cyclic AMP elicited by glucagon. The reversal of system-A induction was observed at relatively low concentration of amino acids, corresponding to plasma values reported in rats given a basal diet. Amino acids were separately tested: substrates of system A were particularly efficient, but so were glutamine and histidine. Non-metabolizable substrates of system A, such as 2-aminoisobutyrate, were also inhibitory, suggesting that a part of the effect of amino acids is independent of their cellular metabolism. Provision of additional energy substrates such as lactate and oleate did not affect induction of system A or the inhibitory effects of amino acids. Thus amino acids do not act by serving as an energy source and by maintaining the integrity of hepatocytes. Inhibition of mRNA synthesis by actinomycin practically abolished the effect of amino acids on the induction of system A by glucagon. The results suggest that amino acids may promote the synthesis of protein(s) affecting the activity of system A either directly at the carrier unit or at an intermediate stage of its emergence.
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PMID:Control by amino acids of the activity of system A-mediated amino acid transport in isolated rat hepatocytes. 241 14

Intestinal adaptation, in terms of increasing intestinal length and weight, usually occurs rapidly after small-bowel resection. However, this response depends on provision of enteral nutrients. If total parenteral nutrition without enteral feeding is prolonged, hypoplasia of the intestinal mucosa results. Adaptation is probably mediated through the presence of luminal nutrients, particularly glutamine, which is preferentially used by the intestine. However, systemic hormonal factors, possibly gastrin, cholecystokinin, and glucagon, also influence intestinal adaptation. Thus, in the management of short-bowel syndromes, enteral nutrition should be added to total parenteral nutrition as soon as possible.
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PMID:Changes in the gastrointestinal tract during enteral or parenteral feeding. 250 20

Compounds with a reported in vivo and in vitro effect on the diabetogenicity of alloxan were studied with regard to the uptake of calcium in mouse islet mitochondria, with the aim of obtaining information on the susceptibility and selectivity of alloxan toxicity. A strong correlation was found between the uptake of calcium in mouse islet mitochondria, which is believed to be associated with the activation of oxidative enzymes involved in energy production and secretion of insulin, and the protection afforded by the injection of D-glucose, D-mannose, L-leucine and glucagon, and by the in vitro administration of cyclic AMP, L-glutamine and L-leucine. The effect of D-glucose was abolished by D-mannoheptulose. A correlation was also seen between reduced mitochondrial uptake of calcium and the potentiation of alloxan cytotoxicity afforded by 1.25-dihydroxycholecalciferol, methylene blue and menadione. The observations suggest an association between functional activity and alloxan cytotoxicity. The selectivity of the cytotoxic action of alloxan is believed to be dependent on a reduced mitochondrial uptake of calcium and an associated reduction of the energy production at low functional activity in the B-cells (e.g. in starvation which is well-known to potentiate the alloxan effect).
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PMID:Alloxan diabetogenicity: determinants of potentiation, protection and B-cell selectivity. 254 7

The mechanism of pyrophosphate (PPi) accumulation in rat liver during acetate metabolism was investigated. Perfusion of the liver with acetate in the presence of noradrenaline and glucagon induced marked accumulation of PPi (2 mumol/g of liver, 200 times that of control). In contrast, perfusion with glutamine, which generates PPi only in the cytosol, caused little accumulation of PPi, even in the presence of the two hormones. The site of PPi accumulation was shown to be the mitochondria by the finding that isolated mitochondria from the liver perfused with acetate and the hormones contained 50 nmol of PPi/mg of protein. The addition of an uncoupler to mitochondria with accumulated PPi caused gradual decrease in their PPi content, with concomitant release of a stoichiometric amount of Ca2+. Similar accumulation of PPi was observed when isolated mitochondria were incubated with acetate and Ca2+. These results show that an increase in cytosolic Ca2+ caused by the co-administration of the two hormones induced uptake of the ion into mitochondria, and that PPi accumulated in mitochondria only when it was generated in the organelles with an elevated concentration of Ca2+. High mitochondrial concentrations of Ca2+ are considered to inhibit inorganic pyrophosphatase through the formation of a stable complex, CaPPi-. Mitochondria with accumulated PPi had normal respiratory activities, and their adenine nucleotide concentrations were increased 2-fold rather than being decreased, the increases also being considered to be caused by their high concentration of Ca2+.
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PMID:Ca2+-induced accumulation of pyrophosphate in mitochondria during acetate metabolism. 255 15


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