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 purpose of this article is to describe briefly the methods by which the intra-mitochondrial volume may be measured both in vitro and in situ, to summarise the mechanisms thought to regulate the mitochondrial volume and then to review in more detail the evidence that changes in the intra-mitochondrial volume play an important part in the regulation of liver mitochondrial metabolism by glucogenic hormones such as glucagon, adrenaline and vasopressin. It will be shown that these hormones cause an increase in matrix volume sufficient to produce significant activation of fatty acid oxidation, respiration and ATP production, pyruvate carboxylation, citrulline synthesis and glutamine hydrolysis. These are all processes activated by such hormones in vivo. I will go on to demonstrate that the increase in matrix volume is brought about by an increase in mitochondrial [PPi]. This is able to stimulate K+ entry into the matrix, perhaps through an interaction with the adenine nucleotide translocase. The rise in matrix [PPi] is a consequence of an increase in cytosolic and hence mitochondrial [Ca2+] which inhibits mitochondrial pyrophosphatase. In the final section of the review I provide evidence that changes in mitochondrial volume may be important in the responses of a variety of tissues to hormones and other stimuli. I write as a metabolist with a working knowledge of bioenergetics rather than the converse, and this will certainly be reflected in the approach taken. If I cause offence to any dedicated experts in the field of bioenergetic by my ignorance or lack of understanding of their studies I can only offer my apologies and ask to be corrected.
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PMID:The regulation of the matrix volume of mammalian mitochondria in vivo and in vitro and its role in the control of mitochondrial metabolism. 264 40

Transport of glutamine and other neutral amino acids across the blood-facing membranes of isolated, dually perfused rat jejunum was measured using a paired-tracer isotope-dilution technique. Glutamine, asparagine, histidine, alanine, and leucine showed mutual inhibition of transport. The major component of physiological glutamine transport was saturable (Km = 0.88 +/- 0.15 mM, Vmax = 454 +/- 49 nmol.g-1.min-1; mean +/- SE), stereospecific and Na-independent and appeared to exhibit symmetry of glutamine transport; it most resembled system L. The minor Na-dependent component of glutamine transport resembled system A, i.e., it transported N-methylaminoisobutyric acid (Km approximately equal to 10 microM, Vmax approximately equal to 1.2 nmol.g-1.min-1). At 0.5 mM glutamine transport was insensitive to insulin and glucagon and was unaffected by perfusate pH (7.0-7.8). Glutamine extracted by the jejunum is rapidly utilized; at physiological blood glutamine concentrations the basolateral glutamine-transporter flux may thus not only restrict intestinal glutamine catabolism but also the consequent release of glutamine-derived ammonia (a substrate and stimulant of ureogenesis) into the portal circulation.
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PMID:Transport of glutamine across blood-facing membranes of perfused rat jejunum. 265 May 66

To investigate the role of hormones as mediators of net skeletal muscle proteolysis following injury, healthy normal male volunteers received a continuous 76-hour infusion of the 3 "stress" hormones: hydrocortisone, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Ten paired studies were conducted. Diets were constant and matched on both occasions. Triple hormone infusion achieved hormone concentrations similar to those seen following mild-moderate injury. After 72 hours of infusion, skeletal muscle intracellular glutamine concentrations were lower in the hormone studies than in the control group (N = 4). Free amino acid concentrations in arterial whole blood and forearm amino acid efflux were little affected by hormonal infusion. Thus, alteration of the hormonal environment by the triple hormone infusion was not a sufficient stimulus to induce all of the changes in skeletal muscle proteolysis observed in critical illness. Since studies utilizing neurohormonal blockade have shown diminished net muscle proteolysis, the stress hormones appear to be necessary but not sufficient for the protein catabolic response to injury.
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PMID:Posttraumatic skeletal muscle proteolysis: the role of the hormonal environment. 267 16

The regulation of hepatic gluconeogenesis was studied in rats made septic by cecal-ligation and puncture technique. Blood glucose was not significantly different in septic rats, but lactate, pyruvate, and alanine were markedly increased. Conversely, blood ketone body concentrations were markedly decreased in septic rats. Both plasma insulin and glucagon were markedly elevated in septic rats. The maximal activities of glucose 6-phosphatase, fructose 1,6-biphosphatase, pyruvate carboxylase, and phosphenolpyruvate carboxykinase were decreased in livers obtained from septic rats suggesting a diminished hepatic gluconeogenesis. Hepatic concentrations of lactate, pyruvate, and other gluconeogenic intermediates were markedly increased in septic rats, whereas those of fructose 2,6-bisphosphate and acetyl-CoA were decreased. The rate of gluconeogenesis from added lactate, pyruvate, alanine, and glutamine was decreased in isolated incubated hepatocytes from septic rats. It is concluded that the diminished capacity of hepatic gluconeogenesis of septic rats could be the result of changes in the maximal activities or regulation of key nonequilibrium gluconeogenic enzymes or both but do not exclude other factors (e.g., toxins).
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PMID:Metabolic control of hepatic gluconeogenesis in response to sepsis. 268 81

The effects of acute administration of either tumour necrosis factor-alpha (cachectin) (TNF) or interleukin-1-beta (IL-1), or of tumour growth (Walker-256 carcinosarcoma), on blood amino acid concentrations and tissue alpha-amino[1-14C]isobutyrate (AIB) uptake in virgin and lactating rats were compared. Both monokines decreased the blood concentrations of those amino acids (serine, glycine, alanine and proline) transported via the A system. Tumour growth decreased the blood concentrations of serine, proline and histidine, whereas the concentrations of glutamine and leucine were increased. IL-1 decreased the intestinal absorption of AIB in all groups studied; TNF or tumour growth had no effect. Tissue AIB uptake was increased (1.5-2.5-fold) in liver, whereas it was decreased in heart and skeletal muscle of the three treatment groups (except skeletal muscle of the IL-1-treated rats). Lactating rats had lower hepatic uptake of AIB compared with livers of virgin rats. IL-1 increased the hepatic uptake of AIB in lactating rats, but not to the values seen in virgin rats treated with IL-1; there was no effect of the cytokine on muscle or mammary-gland uptake. In adrenalectomized rats, the stimulatory effect of IL-1 on hepatic AIB uptake was diminished, whereas that of TNF still persisted. IL-1 caused a marked decrease of AIB uptake in muscle and heart of adrenalectomized rats, which was accompanied by an increase in the blood concentrations of branched-chain amino acids. These effects did not occur with TNF. It is concluded that the effects of the cytokines on tissue amino acid metabolism may depend on a differential endocrine response involving glucagon and/or glucocorticoids.
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PMID:Comparative effects of tumour necrosis factor-alpha (cachectin), interleukin-1-beta and tumour growth on amino acid metabolism in the rat in vivo. Absorption and tissue uptake of alpha-amino[1-14C]isobutyrate. 278 41

Four-day fasting in the conscious dog is associated with enhanced ammoniagenesis in both the gut and kidneys and a switch in the hepatic glutamine balance from net uptake to that of net production. In the present study we examined the role that the rise in portal venous ammonium ions plays in regulating nitrogen metabolism in vivo. Three groups of 18- to 24-h fasted conscious dogs with catheters surgically implanted in the femoral artery and in the hepatic, portal, and renal veins for 17-21 days were studied. On the day of the study, one group (n = 6) received intraportal ammonium acetate at 3.0 mumol.kg-1.min-1 intended to result in portal venous ammonium ion levels slightly above those seen in the 4-day fasted dog. Another group (n = 5) received an equimolar infusion of sodium acetate, and a third group (n = 6) received saline (0.9%) and acted as controls. Organ balances across the liver, extrahepatic splanchnic tissues (gut), and kidneys were estimated by the arteriovenous differences multiplied by blood flows. All of the load of ammonium acetate infused intraportally was taken up by the liver. As a result there was an immediate switch in hepatic glutamine balance from that of net uptake to net production similar to that seen in the 4-day fasted dog. Simultaneously, net hepatic production of urea nitrogen doubled. These occurred with no change in acid-base balance or no change in circulating arterial or portal venous levels of insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Importance of ammonium ions in regulating hepatic glutamine synthesis during fasting. 280 34

We have examined the influence of extracellular pH and calcium concentration on the action of glucagon on isolated rat hepatocytes, perfused liver or plasma membrane preparations. Incubation of rat hepatocytes with 10 nM glucagon at pH 7.4 caused an immediate increase in cAMP concentrations (8-fold), and this rise was almost 50% lower at acidic extracellular pH (6.9). This effect of pH could not be explained by an alteration of the hormone binding to its receptor for glucagon concentrations higher than 1 nM. The effect of acidosis on cAMP production was still present with non-hormonal effectors, such as 10 microM Gpp[NH]p, 30 microM forskolin or 10 mM NaF. This suggests a direct action of acidosis on the regulatory component Ns and/or on the catalytic subunit of adenylate cyclase. Acidic pH also depressed mitochondrial processes responsive to glucagon (NAD(P)H fluorescence, glutamine breakdown). Whatever the experimental model, calcium appeared to be required for maximal stimulation of cAMP production by glucagon. On perfused rat liver, glycogenolysis was depressed in the absence of extracellular calcium in the perfusate. In isolated hepatocytes, the stimulation of phosphorylase alpha activity by glucagon was modulated by extracellular calcium concentrations lower than 0.2 mM. This suggests that, although glucagon action is chiefly cAMP-mediated, its effect on calcium mobilization (affecting various cellular process, including cAMP production itself) should also be taken into account. This work also confirmed the importance of calcium in the stimulation of mitochondrial metabolism of glutamine by glucagon.
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PMID:Modulation of glucagon effects by changes in extracellular pH and calcium. 282 79

The effects of increasing concentrations of leucine (0.2, 2.0, and 15.0 mmol/liter) on glucagon secretion from the perfused rat pancreas were examined at various glucose levels (0, 3.3, or 8.3 mmol/liter) and in the absence or presence of either arginine (5.0 mmol/liter) or glutamine (10.0 mmol/liter). At a low glucose concentration (3.3 mmol/liter), leucine caused a dose-related biphasic increase in glucagon output in the absence of arginine, but only a transient increase in the presence of the latter amino acid. These positive responses were markedly reduced and, on occasion, abolished at a high glucose concentration (8.3 mmol/liter). Moreover, at a low glucose concentration (3.3 mmol/liter) and in the presence of arginine, the highest concentration of leucine (15.0 mmol/liter) provoked a sustained and reversible inhibition of glucagon release. Likewise, leucine (15.0 mmol/liter) reversibly inhibited glucagon secretion evoked by glutamine in the absence of glucose. Thus, leucine exerted a dual effect on the secretion of glucagon, the inhibitory effect of leucine prevailing at a high concentration of the branched chain amino acid and when glucagon secretion was already stimulated by arginine or glutamine. At a physiological concentration (0.2 mmol/liter), however, leucine was a positive stimulus for glucagon release, especially in the absence of another amino acid. Concomitantly, leucine was always a positive stimulus for both insulin and somatostatin secretion. The intimate mechanisms involved in the dual effect of leucine on glucagon secretion remain to be elucidated.
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PMID:Multiple effects of leucine on glucagon, insulin, and somatostatin secretion from the perfused rat pancreas. 285 40

The role of nutrients and hormones in the regulation of glucagon release is investigated in pancreatic A cells purified by autofluorescence-activated cell sorting. Purified A cells lack secretory activity in 1-h incubation at 1.4 mM glucose. Their release mechanism can be activated by arginine, alanine, and glutamine, alone or in combination. Glucose inhibits amino acid-induced glucagon release through a direct insulin-independent action upon pancreatic A cells. Nutrient-induced glucagon release is suppressed by somatostatin and amplified by (Bu)2cAMP or epinephrine. The epinephrine stimulus is inhibited by 10(-11) M somatostatin and abolished by 10(-10) M of this peptide. The effects of somatostatin and epinephrine are associated with parallel changes in cellular cAMP levels, which is not the case for the variations induced by amino acids or glucose. It is confirmed that calcium is an essential requirement for glucagon release. In contrast to its exquisite sensitivity for somatostatin, the glucagon release process is relatively insensitive to insulin during a 1-h exposure. The hormone affects solely epinephrine-induced glucagon release and its inhibitory action is partial and only observed at 10(-7) M. This suppressive effect of insulin is not attributable to variations in glucose handling but appears associated with the stimulatory effect of epinephrine. It is concluded that a nutrient-induced signal interacts with a hormone-inducible cAMP signal to activate the secretory process in pancreatic A cells.
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PMID:Interplay of nutrients and hormones in the regulation of glucagon release. 286 20

Protein catabolism following injury is associated with elevated levels of the stress hormones cortisol, glucagon, and the catecholamines. To study the effect of hormonal blockade on catabolic responses to surgery, 16 dogs underwent general anesthesia, a standard abdominal operation, and implantation of aortic and caval catheters. Five received phentolamine and propranolol continuously, at doses which block catecholamine effects. To prevent the rise in both catecholamines and cortisol, 6 received a high epidural anesthetic (T4-S3), started preoperatively and continued for 24 hr. Five dogs served as controls. Hindquarter amino acid flux was measured at 6 and 24 hr post-op. Pre- and post-op skeletal muscle biopsies were analyzed for amino acids. Urinary nitrogen was measured over 24 hr. Urinary nitrogen excretion was unaffected by treatment, but urinary creatinine fell from 0.039 +/- 0.002 g/24 hr X kg for controls to 0.03 +/- 0.002 for the epidural group and 0.031 +/- 0.001 for alpha and beta blockade (P less than 0.05). Hindquarter amino acid nitrogen efflux was decreased from -19.05 +/- 4.06 mumole/min X kg in controls to -8.98 +/- 0.86 in the epidural and -6.89 +/- 1.21 in the alpha- and beta-blockade groups (P less than 0.05). The urinary nitrogen loss, glutamine efflux, and fall in muscle glutamine produced by the operation were not prevented by either form of hormonal blockade, but hindquarter nitrogen efflux was diminished. Hormonal blockade inhibits net skeletal muscle protein catabolism without altering whole-body nitrogen loss. Hormones and other factors must be responsible for the increased ureagenesis that occurs following injury.
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PMID:Hormonal blockade modifies post-traumatic protein catabolism. 286 76


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