Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viable Hepatocytes were isolated from adult canine liver by in situ collagenase perfusion, and cultured on collagen coated borosilicate glass plates (100 X 200mm) at confluent cell density. The medium of hepatocytes in the primary culture was L-15 supplemented with aprotinin 5000U/L, proline 30mg/L, insulin 10(-8)M, dexamethasone 10(-8)M, glucagon 10(-8)M, and h-EGF 10ng/ml. Long-stroke type bioartificial liver module consisted of 200 glass plates with hepatocytes. It contained 6 billion primary cultured cells in total, that is almost equivalent to 30% of the normal canine liver. All hepatocytes in the module were quite viable during 2 weeks in the perfusion culture, and maintained various liver functions at a high level. Gluconeogenesis was 368.0 +/- 15.4mg/module/hr, albumin synthesis was 19.1 +/- 2.5mg/module/day, ureogenesis was 3.7 +/- 0.1mg/module/hr, and ammonia metabolism was 8.4mg/module/hr. Moreover, those functions were maintained at least 2 weeks in the canine plasma as well as in the culture medium with hormones. This hybrid bioartificial liver may exert various liver functions like a liver in situ.
 ...
PMID:[Hybrid bioartificial liver using canine hepatocytes in primary culture]. 276 24

The results of the few studies on the effect of the thyroid status on nitrogen metabolism have been inconclusive and/or contradictory. In an attempt to elucidate this important relationship, we have studied the effect of experimental hypo- and hyperthyroidism on urea biosynthesis and related processes. We have found that the capacity of the liver to synthesize urea was increased in hypothyroid rats, as were the activities of the urea cycle enzymes; there were also changes in the activities of some related enzymes and in the levels of intermediates and amino acids. Isolated hepatocytes from these rats showed an increased capacity for urea synthesis. In hyperthyroid rats the picture was more complicated, since there was no change in the urea-synthesizing capacity of the liver, although there were changes in some enzymes and metabolites. Our results suggest that there may be more endogenous proteolysis in hypothyroidism which would increase ammonia production, the ammonia being used primarily for urea biosynthesis and, to a lesser extent, for glutamate and aspartate synthesis. These overall effects might be the result of an increase in glucagon and/or cAMP, which, as is well known, increase the urea-synthesizing capacity of liver. In hyperthyroidism, on the other hand, the changes in nitrogen metabolism could be the result of an increase in protein synthesis, a decrease in catabolic activity, or both.
 ...
PMID:Effect of thyroid hormones on urea biosynthesis and related processes in rat liver. 284 5

The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0-5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal-induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia.
 ...
PMID:Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. 289 85

The effects of subclinical NH3 toxicity on circulating and regulatory hormone concentrations were investigated in seven Hereford steers. Ammonium chloride (NH4Cl) was infused via a right jugular vein catheter at a rate of 12 mumol NH4Cl.kg BW-1.min-1 for 240 min. This was preceded (PRE) and followed (POST) by saline infusions of 120 and 180 min, respectively. Blood samples were taken at 20-min intervals via a left jugular vein catheter. Metabolite and hormone concentrations during NH4Cl and POST periods were compared to PRE values using the Student's t-test procedure. Plasma NH3 was elevated rapidly (P less than .001) and peaked at 503 micrograms/dl 220 min into NH4Cl infusion. Plasma urea-N and glucose increased (P less than .001) 39 and 12%, respectively, during NH4Cl infusion and remained elevated 180 min POST. Whole blood L-lactate concentrations peaked (P less than .05) at 18% above PRE between 160 and 240 min into the NH4Cl infusion and gradually returned to PRE values, whereas pyruvate levels were not altered (P greater than .10). Plasma nonesterified fatty acids peaked (P less than .001) at 94% above PRE levels 40 min into NH4Cl infusion, thereafter declining to PRE concentrations. Whole blood acetoacetate and beta-hydroxybutyrate concentrations were not altered (P greater than .10) by NH4Cl administration. Plasma insulin concentration decreased (P less than .05) 26 to 46% during NH4Cl infusion and increased (P less than .05) 89 to 122% during POST. Plasma glucagon levels were not altered by NH4Cl infusion, so molar insulin:glucagon ratio changes resembled those of insulin. Plasma epinephrine, norepinephrine and dopamine did not vary (P greater than .10) with treatment. These results support the hypothesis that the hyperglycemia observed during hyperammonemia may result from an under-utilization of glucose by insulin-sensitive tissues.
 ...
PMID:Subclinical ammonia toxicity in steers: effects on blood metabolite and regulatory hormone concentrations. 306 22

The effects of chronic uraemia on glucose production and nitrogen release (urea plus ammonia formation) from alanine, glutamine or serine in isolated rat hepatocytes were studied. Uraemia increased the rate of formation of urea plus ammonia from all three amino acids by 38-93% when they were present at a final concentration of 10 mmol/l. At lower concentrations (2 mmol/l) the rate of nitrogen release was not significantly increased. Hepatocytes from normal rats whose food intake had been restricted to the level of that of uraemic rats did not show the increased rates of nitrogen release. The increased rates of nitrogen release with hepatocytes from uraemic rats were not accompanied by increased rates of glucose synthesis. Instead, accumulation of metabolic intermediates occurred: lactate and pyruvate (alanine or serine as substrates) and glutamate (glutamine as substrate). Livers of uraemic rats had increased activities of glutaminase (30%) and serine dehydratase (100%). Hepatocytes from normal rats treated with phlorhizin to increase the plasma glucagon/insulin ratio behaved in a similar manner to hepatocytes from uraemic rats. They had increased serine dehydratase activity, and increased rates of utilization of serine or glutamine. The possible implications of these findings for human uraemia are discussed.
 ...
PMID:Effects of chronic uraemia on the formation of glucose and urea plus ammonia from L-alanine, L-glutamine and L-serine in isolated rat hepatocytes. 308 21

The isolated perfused rat pancreas was used to investigate how adrenergic influences within the pancreas might mediate ammonia-induced glucagon secretion. The addition of 2 mM ammonia to the perfusate increased norepinephrine release and glucagon secretion in the effluent. Upon cessation of ammonia addition, a pronounced burst of glucagon release was observed. Alpha-adrenergic blockade with phentolamine (10 microM) blocked the glucagon response to ammonia. Beta-adrenergic blockade with propranolol (10 microM) had no significant effect on the amount of glucagon release induced by ammonia. Depletion of norepinephrine from sympathetic nerve terminals by pretreatment with 6-hydroxydopamine lowered the pancreatic norepinephrine content to less than 16% of the control value and diminished the glucagon and norepinephrine response to ammonia almost completely. The burst of glucagon release after the removal of ammonia was inhibited to 2% of the control value by phentolamine and to 57% by propranolol. Pretreatment with 6-hydroxydopamine reduced the burst of glucagon secretion to 28% of the control value. Neither phentolamine nor propranolol reduced the magnitude of the ammonia-induced suppression of insulin secretion. We conclude that the effect of ammonia on glucagon release from the isolated rat pancreas is mediated by intrapancreatic adrenergic control.
 ...
PMID:Adrenergic control of the glucagon response to ammonia in the perfused rat pancreas. 314 94

Hyperammonemia is a well-recognized metabolic abnormality which occurs in cirrhotic patients with advanced liver dysfunction. We recently documented that hyperglucagonemia that occurs as a result of hepatic glycogen depletion may be responsible for this hyperammonemia by promoting gluconeogenesis to provide glucose as a fuel for functioning of several organ systems. Thus, hepatic glycogen depletion may be the initial process responsible for hyperammonemia. Since the glucose rise following intravenous glucagon administration is a reflection of hepatic glycogen breakdown, we studied the effect of glucagon (1 mg) injection on plasma glucose, insulin and ammonia levels after an overnight fast in cirrhotic patients and normal subjects. Glucose rise was significantly stunted, and ammonia rise was significantly greater in patients with advanced liver dysfunction as compared to normal subjects. Furthermore, the smaller the glucose increment, the earlier the ammonia rise. The smallest glucose responses were seen in the patients with the highest basal plasma ammonia levels. Finally, significant negative relationships were noted between the glucose response to glucagon administration (delta glucose) and the degree of liver dysfunction as reflected by Composite Clinical Laboratory Index, as well as basal ammonia and ammonia responses (delta ammonia) on the other. Therefore, this study suggests that hepatic glycogen depletion may be the initial event leading to elevated plasma ammonia concentrations in hepatic cirrhosis.
 ...
PMID:The association of hepatic glycogen depletion with hyperammonemia in cirrhosis. 330 64

In primary cultures of rat hepatocytes the glucagon-dependent induction of phosphoenolpyruvate carboxykinase was studied in the presence of putative local hormone and substrate modulators which form clear concentration gradients during liver passage such as adenosine, ketone bodies and ammonia. 1) Adenosine inhibited the induction of phosphoenolpyruvate carboxykinase in a concentration-dependent manner between 50 and 200 microM up to 4 h after glucagon application; AMP had similar, adenine, inosine and guanosine had no effect. Adenosine was almost totally metabolized by the liver cells during the first 4 h of the induction period. The inhibitory action of adenosine was also observed using dibutyryl-cAMP or 8-bromo-cAMP as inducer; it could not be prevented by the adenosine receptor antagonist caffeine nor could it be mimicked by the selective adenosine receptor agonist N6-(phenylisopropyl)adenosine. 2) Acetoacetate suppressed the induction of phosphoenolpyruvate carboxykinase in a concentration-dependent manner between 5 and 20mM during the first 4 h after glucagon addition. beta-Hydroxybutyrate showed no effect. Neither starting with acetoacetate nor with beta-hydroxybutyrate did the cell cultures establish the thermodynamic equilibrium between the two compounds. 3) Ammonia did not affect induction of phosphoenolpyruvate carboxykinase at concentrations up to 2mM. Ammonia was converted to urea within the first 4 h; yet it remained at clearly hyperphysiological concentrations in the medium during that period. It is concluded that the glucagon-dependent induction of phosphoenolpyruvate carboxykinase was modulated by the local hormone adenosine via a mechanism not involving adenylate cyclase and by acetoacetate via an unknown mechanism. The inhibitory action of adenosine may, that of acetoacetate can hardly be physiologically relevant.
 ...
PMID:Modulation of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase by adenosine, but not ketone bodies or ammonia in rat hepatocyte cultures. Possible significance for the zonal heterogeneity of liver parenchyma. 344 1

The provision of small amounts of glucose during fasting is known to spare body protein and to attenuate markedly the metabolic response to starvation. These actions, which are not shared by fat, are generally thought to depend on the ability of exogenous glucose to stimulate insulin secretion. To determine whether fructose, a very weak insulin secretagogue, will also conserve nitrogen and alter the response to fasting, we infused small amounts of fructose, 100 g/d (375 kcal), into 7 obese subjects during a 10-day fast: 4 received fructose days 7 to 10, and 3 received fructose days 1 to 7. Fructose virtually abolished (all P less than 0.05-0.01) the fasting induced: (a) fall in glucose and insulin and rise in glucagon, (b) fall in triiodothyronine, (c) ketosis and acidosis, (d) increased ammonia excretion, (e) hyperuricemia (and hypouricosuria), and (f) fall in plasma alanine and rise in branched chain amino acids. Fructose also significantly reduced urinary sodium loss. Moreover, fructose exerted a prominent protein-sparing action, even though plasma insulin concentrations never exceeded postabsorptive levels. Excretion of total nitrogen was reduced by 40% to 50% during periods of fructose infusion, reflecting significant suppression of both urea and ammonia generation (all P less than 0.05-0.01). Most plasma glucogenic amino acids rose significantly during fructose administration. We conclude that low-dose fructose infusion essentially abolishes the entire hormone-substrate response to fasting, and spares body protein without raising insulin above postabsorptive levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nitrogen conservation in starvation revisited: protein sparing with intravenous fructose. 351 Mar 63

Effects of ammonia on glucagon and insulin secretion from the perfused pancreas of cirrhotic rats were investigated to clarify the occurring mechanism of hypersecretion of pancreatic glucagon in liver cirrhotics. The results were as follows: During ammonia loading, insulin secretion was inhibited in a dose-related manner, whereas glucagon secretion was gradually increased at high concentrations of ammonia (2 mM) in control rats; this tendency was augmented in the presence of alpha-ketoglutarate in cirrhotic rats. On cessation of ammonia loading, a transient but definite increase in glucagon and insulin secretion was observed. Basal plasma glucagon and ammonia levels as well as basal glucagon secretion from the perfused pancreas of cirrhotic rats were significantly higher than in control rats. Basal insulin secretion from the perfused pancreas of cirrhotic rats was not different in spite of high levels of plasma insulin. Glucagon secretory response to glucose and arginine from the perfused pancreas of cirrhotic rats was higher than in the control pancreas, whereas insulin secretion was lower. In these cirrhotic rats, an increase in the number of islet cells, particularly A cells, was observed. These data suggested that hypersecretion of pancreatic glucagon which was responsible for hyperglucagonemia in cirrhotic rats might be attributed to high levels of ammonia and alpha-ketoglutarate in blood as well as to the fluctuation of abnormal ammonia concentration in blood and to the hypertrophy of islets, particularly of the A cell group due to hypersecretion.
 ...
PMID:Effect of ammonia on glucagon secretion from the perfused pancreas of cirrhotic rats. 352 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>