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)

We investigated the roles of insulin and glucagon as mediators of changes in glucose and alanine kinetics during the hypermetabolic response to injury in 10 burn patients by infusing somatostatin with and without insulin replacement. Glucose and alanine kinetics were measured by primed-constant infusions of 6,6-d2-glucose and [3-13C]alanine. The basal rate of glucose production and alanine flux were significantly elevated in all patients. Lowering both hormones simultaneously caused an insignificant reduction in glucose production, but plasma glucose rose significantly (P less than 0.01), because of reduced clearance. Alanine flux and total plasma amino nitrogen increased significantly (P less than 0.05) above basal. Selectively lowering glucagon concentration decreased glucose production (P less than 0.05), and exogenous glucose was infused to maintain euglycemia. Alanine flux and total plasma amino nitrogen remained unchanged. In severely burned patients hyperglucagonemia stimulates increased glucose production, basal insulin suppression glucose production, stimulates basal glucose clearance, and is important for regulation of plasma amino acid concentrations, and the selective lowering of glucagon while maintaining basal insulin constant normalized glucose kinetics.
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PMID:Role of insulin and glucagon in the response of glucose and alanine kinetics in burn-injured patients. 287 83

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.
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PMID:Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. 289 85

The in vivo flux rates of glucose (6-3H-glucose) and of alanine (U-14C-alanine) were measured in insulin-dependent chronically diabetic dogs which were infused with insulin employing a bedside-type artificial B cell and either the peripheral or the portal venous route. In comparison with non-diabetic control animals the diabetic dogs had near-normal patterns of glucose metabolism and pancreatic glucagon regardless of the route of insulin administration. They also showed reduced basal portal but moderately elevated peripheral insulin levels on peripheral and near-normal peripheral values on portal insulin infusion. Both concentration and production rates of alanine were reduced on peripheral (0.142 +/- 0.016 mmol/l, 4.73 +/- 0.49 mumol.kg-1.min-1, p less than 0.05) but normal on portal insulin (0.206 +/- 0.030 mmol/l, 6.33 +/- 0.63 mumol.kg-1.min-1). The alanine clearance was slightly elevated or normal in the diabetic dogs, and the glucose production from alanine showed a strongly delayed response to an exogenous glucose load on either route of insulin administration. It is concluded that the peripheral hyperinsulinism during posthepatic insulin administration stimulates glucose utilisation to a normal extent, but inhibits the provision of amino groups in resting muscle. Alanine synthesis is thereby reduced, and the carbon moieties are shunted from glucose into circulating lactate. Long-term studies are needed to elucidate the role of the liver under these conditions.
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PMID:The effect of prehepatic insulin administration on alanine flux rates in diabetic dogs. 331 97

1. Lysine and alanine uptake by pig enterocytes has been measured in piglet mid intestine both during normal development and 3 days after injection of dexamethasone and epidermal growth factor (EGF) into 3-day-old animals. 2. Alanine uptake measured in the presence of sodium increased markedly during the first 4 weeks of post-natal life. Similar effects on alanine uptake could be produced through injection of dexamethasone, but not EGF, into 3-day-old piglets. Alanine uptake measured in the absence of sodium and lysine uptake measured in the presence of sodium remained unchanged during development and unaffected by injection of dexamethasone or EGF. 3. Enterocytes capable of transporting alanine in the presence of sodium were found, by quantitative autoradiography, to cover the top 400 micron of the villus in 6-day-old and 3-4-week-old control pigs. Alanine concentrations in villus tip enterocytes in 3-4-week-old pigs were four times those found in 6-day-old animals. Qualitative examination of selected villi, however, showed alanine uptake taking place over a considerably greater area of villus surface in 6-day-old compared with 3-4-week-old animals. 4. Injection of dexamethasone and EGF into 3-day-old piglets caused an increase in crypt depth without apparent change in crypt cell proliferation. The rate at which enterocytes migrated out of the crypt and the length of individual villi also remained unchanged by dexamethasone or EGF injection. 5. Dexamethasone produces its effect on alanine uptake by acting on older enterocytes present on the upper part of the villus. These enterocytes can be shown, by calculations based on enterocyte migration rate, to have already been present on the villus at the time the pig was born. 6. The above findings are discussed in relation to the ability of villus as well as crypt enterocytes to change their programme of differentiation in response to external stimuli. The particular ability of dexamethasone to induce system A type carrier function is further discussed in relation to normal changes found to occur during neonatal development. It is finally suggested, as a working hypothesis, that endogenous glucagon might act as the final mediator of both developmentally controlled and dexamethasone-induced changes in amino acid transport.
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PMID:Dexamethasone selectively increases sodium-dependent alanine transport across neonatal piglet intestine. 350 67

The effect of glucagon on the capacity of urea-N synthesis was examined in 24 rats as a function of time. First, the conditions for saturation of urea synthesis under glucagon influence were studied by the kinetics of urea-N synthesis rate in relation to arterial blood alpha-amino-N concentration between 5 and 17 mmol/l in 21 nephrectomized rats given zinc-glucagon (20 micrograms s.c. per day) for 14 days. Alanine was infused so that steady state concentrations of total alpha-amino-N was attained in each rat. The urea-N synthesis rate was calculated as accumulation in total body water corrected for intestinal hydrolysis. The relationship suggested a barrier limited substrate inhibition kinetics, as earlier found in control rats, and data were examined accordingly by non-linear regression analysis. The estimated kinetic constants were: Vmax = 71 mumol/(min X 100 g body wt), Km = 5.4 mmol/l, Ki = 2.4 mmol/l, and the barrier = 4.4 mmol/l. Vmax was increased three times compared with controls. The capacity of urea-N synthesis, i.e. the zenith of the relation, was attained in the concentration interval 7.5 to 12.0 mmol/l, as in controls. The capacity of urea-N synthesis was determined during i.v. infusion of zinc-glucagon (0.15 microgram per min) and after 2, 8, and 14 days of daily s.c. injections of 20 micrograms zinc-glucagon. Rats given zinc-protamine solution were controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Time dependent stimulating effect of glucagon on the capacity of urea-N synthesis in rats. 355 84

This study examined ketosis in response to 90 min of running before and after the ingestion of 50 g glucose or 50 g L-alanine in thirty-three athletes. Everyone ran 20 km at 07.30 h and then rested, while fasting, till 16.00 h. There were four test groups: 'glucose-before', 'glucose-after', 'alanine-before' and 'alanine-after' according to whether glucose or alanine was ingested at 07.00 h, or 09.00 h. Controls did not ingest either test substance. The control 3-hydroxybutyrate concentration rose from 0.23 +/- 0.03 mmol/l (S.E. of mean) at 07.00 h to 0.74 +/- 0.27 mmol/l at 12.00 h, and 0.94 +/- 0.33 mmol/l at 16.00 h. Glucose ingestion before or after exercise did not influence post-exercise ketosis significantly, despite high insulin: glucagon ratios, low free fatty acid concentrations and hyperglycaemia. Alanine significantly lowered the 3-hydroxybutyrate levels, especially after exercise (to 0.14 +/- 0.07 mmol/l at 12.00 h; P less than 0.05) despite reversed insulin: glucagon ratios. This suggests that hepatic responsiveness to portal hyperglycaemia and the main hormones of metabolism is altered immediately after exercise, presumably to promote muscle glycogen synthesis in preference to liver glycogen synthesis.
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PMID:Post-exercise ketosis in post-prandial exercise: effect of glucose and alanine ingestion in humans. 388 75

The effect of alanine on ketone body levels, independent of hormonal changes, in normal man has been investigated. Five normal subjects were given somatostatin infusions (200 micrograms/hour) for 3 hr. After 1 hr alanine or isotonic saline was infused for 2 hr. With saline blood beta-hydroxybutyrate and acetoacetate levels rose steadily to a peak of 0.230 plus or minus 0.053 and 0.112 plus or minus 0.023 mmole/l respectively. With alanine beta-hydroxybutyrate and acetoacetate levels plateaued at 0.099 plus or minus 0.020 and 0.055 plus or minus 0.006 mmole/l respectively. Alanine levels reached nearly 1 mmole/l but a significant effect on ketone body levels was apparent at physiologic levels (less than 0.6 mmole/l). Plasma fatty acid and glycerol levels did not change significantly. Insulin C-peptide and glucagon levels were suppressed to a similar extent in both experiments. These results support the view that alanine suppresses ketogenesis in man by a direct hepatic effect independent of insulin and glucagon. It is suggested that this forms part of a negative feedback substrate cycle between alanine and ketone bodies.
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PMID:The antiketogenic effect of alanine in normal man: evidence for an alanine-ketone body cycle. 611 56

The effects of amino acids, exogenous islet hormones and acetylcholine on cyclic nucleotide metabolism and amylase secretion in the isolated mouse pancreas have been investigated. The changes in levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) were measured at different times during exposure of pancreatic fragments to amino acids (L-alanine and L-arginine), islet hormones (insulin and glucagon) or acetylcholine (ACh). L-Alanine (1-20 mM) evoked a transient increase in cyclic AMP concentration accompanied by an initial decrease and subsequent increase in the tissue concentration of cyclic GMP. L-Arginine (1-20 mM) induced a complex triphasic change in cyclic AMP concentrations involving an initial rise and a delayed sustained elevation. The changes in levels of cyclic GMP increased only transiently. The effects of insulin (10(-6) M) and to some extent glucagon (5 X 10(-7) M) resembled those seen with L-arginine. The effects of amino acids and islet hormones were all dose-dependent. ACh (10(-7) M) elicited a marked reduction in cyclic AMP concentration and this was accompanied by a concomitant increase in the level of cyclic GMP. The amino acids and the islet hormones had no significant effect on amylase secretion whereas ACh, of course, evoked a large increase in amylase output. The results with the amino acids and islet hormones reveal a clear dissociation between cyclic nucleotide changes and amylase secretion and further suggest that the marked reciprocal changes in cyclic AMP and cyclic GMP concentrations may constitute an important physiological role for the cyclic nucleotides to regulate amino acid transport in the pancreas.
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PMID:Effects of amino acids, glucagon, insulin and acetylcholine on cyclic nucleotide metabolism and amylase secretion in isolated mouse pancreatic fragments. 619 59

A new technique was developed for the isolation of chicken liver parenchymal cells. Glucose produced from 10 mM lactate was proportional to the amount of cells present. In the time-course study, gluconeogenesis from lactate and fructose was linear up to 60 min. Fructose proved to be the best substrate. Fructose was converted to glucose at the highest rate; this was followed by lactate, pyruvate, and xylitol. Alanine, glycerol, propionate, alpha-ketoglutarate, and succinate proved to be poor substrates. There was no statistical difference between the results obtained with hepatocytes obtained from fed or fasted chickens. The isolated hepatocytes responded to glucagon, dibutyryl-cAMP, and epinephrine. The dose-response for glucagon was a sigmoid-curve and the half-maximum stimulation was given by approximately 1 x 10(-2) micrometers hormone. The same type of curve was obtained with dibutyryl-cAMP, but the half-maximum stimulation was achieved at around 1.0 micrometer. The response to epinephrine was marginal. In the time-course experiment, prior to glucagon stimulation, glucose accumulated at a linear rate (slope = .2484). After the addition of the hormone, the level of cAMP increased by about 30% in the first minute and reached a peak (100%) in about 2 min; thereafter, it decreased to the level prior to the stimulation by the hormone. Two minutes after the addition of glucagon there was a significant increase in the rate of gluconeogenesis; this continued for another 3 min and then at a slower pace (slope = .2566).
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PMID:A technique for the isolation of chicken hepatocytes and their use in a study of gluconeogenesis. 627 59

Alanine-2-oxoglutarate aminotransferase activity in mouse liver is stimulated by the intravenous injection of glucagon. The stimulation is abolished by pretreatment with actinomycin D indicating that the increased activity is probably due to new enzyme formation. Administration of dibutyryl cyclic AMP, isoproterenol, an activator of adenyl cyclase and theophylline, an inhibitor of phosphodiesterase also increases the enzyme activity suggesting the involvement of cyclic AMP in glucagon-mediated increase of enzyme activity.
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PMID:Effect of glucagon on alanine 2-oxoglutarate aminotransferase. 631 82


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