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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although glucose intolerance occurs as a consequence of chronic renal failure, improvement of a diabetic state by deterioration of renal function is a well known phenomenon. Recently occasional cases of spontaneous hypoglycemia in patients with chronic renal failure have been reported; two such cases and the results of metabolic studies are described in this paper. Pituitary, thyroid and adrenal function appeared to be normal. The results of an oral glucose tolerance test were normal; an appropriate insulin response was demonstrated in one patient, and a slightly elevated basal insulin value with a delayed insulin response to oral administration of glucose was demonstrated in the other. An insulin tolerance test did not support the hypothesis of increased insulin sensitivity as a factor, and the growth hormone response to hypoglycemia was normal. An intravenous glucagon test caused a subnormal increase in plasma glucose concentration, and the intravenous administration of tolbutamide produced hypoglycemia without an increase insulin sensitivity as a factor, and the growth hormone response to hypoglycemia was normal. An intravenous glucagon test caused a subnormal increase in plasma glucose concnetration, and the intravenous administration of tolbutamide produced hypoglycemia without an increase in insulin values. The plasma alanine concentration was low and the proinsulin/insulin ratio was increased. The origin of this hypoglycemia is not clear but is probably multifactorial. However, low hepatic glycogen stores and inadequate gluconeogenesis due to substrate deficiency seem to be involved.
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PMID:[Spontaneous hypoglycemia and chronic kidney insufficiency]. 64 92

Ten term and eleven preterm newborn infants with appropriate weights for their gestational age were infused for one minute with L-alanine (150 mg/kg) at the age of 29 to 76 hours (mean 48 hours) and circulating levels of glucose, lactate, pyruvate, D-betahydroxybutyrate (D-BOHB), insulin and glucagon were monitored. Plasma glucose concentrations increased from 2.7 +/- 0.16 (mean +/- S.E.M.) to 3.7 +/- 0.2 mmol/l after 50 min (p less than 0.01) in term infants. In preterm infants, after an initial decrease of the glucose level from 3.1 +/- 0.16 to 2.6 +/- 0.16 mmol/l (p less than 0.05), it returned to the baseline level at 50 min: 3.0 +/- 0.2 mmol/l. The blood concentration of D-BOHB decreased in term infants from 192 +/- 37 to 112 + 6 micrometer/l (p less than 0.01) after 40 min. In preterms, its decrease was not significant (p greater than 0.05). Plasma glucagon level rose from 53 +/- 5 to 70 +/- 8 pmol/l after ten minutes (p less than 0.01) in terms infants and from 61 +/- 6 to 75 +/- 9 after 20 min (p less than 0.01) in preterm infants. There were no significant changes in plasma insulin concentrations in either group. Forty minutes after L-alanine infusion, I/G ratios were lower in preterm infants (1.26 +/- 0.14) than in term infants (1.71 +/- 0.25) (p less than 0.01). There was no relationship between the glycemic responses to L-alanine and the basal levels of D-BOHB. The data suggest that the glycemic effect of L-alanine infusion and circulating glucagon depends upon a specific stage in maturation. The antiketogenic effect of L-alanine infusion is observed in term infants as in adults.
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PMID:Effect of intravenous L-alanine administration on plasma glucose, insulin and glucagon, blood pyruvate, lactate and beta-hydroxybutyrate concentrations in newborn infants. Study in term and preterm newborn infants. 65 7

Blood substrate and hormone concentration were determined in 16 children with Reye syndrome prior to and following administration of hypertonic glucose. Baseline concentrations of lactate, pyruvate, alanine, glutamine, glutamate, proline, hydroxyproline, lysine, and aspartate were elevated (p less than 0.01), whereas citrulline and arginine were low. All substrate concentrations were below or within the normal range following 36 hours of therapy except those of lactate, pyruvate, and aspartate. Urea nitrogen excretion was reduced (p less than 0.05) on the second day of therapy. Plasma concentrations of insulin and growth hormone increased and glucagon decreased during the first day. Cortisol remained elevated throughout the study period. We conclude that the high circulating concentrations of substrates are the result of both increased mobilization and decreased clearance and that hypertonic glucose infusion suppresses substrate mobilization. A primary abnormality of the mitochondria could explain the metabolic perturbations that occurred. A possible relationship between the encephalopathy in this disorder and an insult to both brain and brain capillary mitochondria is discussed.
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PMID:Metabolic response to hypertonic glucose administration in Reye syndrome. 66 61

Spontaneous fasting hypoglycemia developed in four nondiabetic patients with end-stage renal failure. All were undergoing long-term maintenance hemodialysis and three patients were anephric. Hypoglycemia was generally accompanied by severe metabolic acidosis and, in three patients, lactic acidemia. Abnormalities of hepatic structure and/or function were present in three patients. In one patient, hypoglycemia was refractory to exogenous glucagon, failed to respond to alanine, glycerol, or galactose, and was associated with suppressed plasma insulin and elevated plasma glucagon levels. Fasting hypoglycemia appeared to result from several mechanisms. In at least two patients, fasting hypoglycemia and lactic acidosis resulted from impaired hepatic gluconeogenesis in association with impaired or absent renal glucose production. Additionally, substrate limitation probably contributed to hypoglycemia in several patients.
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PMID:Spontaneous hypoglycemia in chronic renal failure. 68 26

The aim of the present experiments was to determine the effects of basal glucagon on glucose production after induction of prolonged insulin lack in normal conscious dogs fasted overnight. A selective deficiency of insulin or a combined deficiency of both pancreatic hormones was created by infusing somatostatin alone or in combination with an intraportal replacement infusion of glucagon. Glucose production (GP) was measured by a primed constant infusion of [3H-3]glucose, and gluconeogenesis (GNG) was assessed by determining the conversion rate of circulating [14C]alanine and [14C]lactate into [14C]glucose. When insulin deficiency was induced in the presence of basal glucagon the latter hormone caused GP to double and then to decline so that after 4 h it had returned to the conrol rate. The conversion of alanine and lactate into glucose, on the other hand, increased throughout the period of insulin lack. Withdrawal of glucagon after GP had normalized resulted in a 40% fall in GP, a 37% decrease in GNG, and a marked decrease in the plasma glucose concentration. Induction of insulin deficiency in the absence of basal glucagon resulted in an initial (30%) drop in GP followed by a restoration of normal GP after 2--3 h and moderately enhanced glucose formation from alanine and lactate. It can be concluded that (a) the effect of relative hyperglucagonemia on GP is short-lived; (b) the waning of the effect of glucagon is attributable solely to a diminution of glycogenolysis because GNG remains stimulated; (c) basal glucagon markedly enhances the GNG stimulation apparent after induction of insulin deficiency; and (d) basal glucagon worsens the hyperglycemia pursuant on the induction of insulin deficiency both by triggering an initial overproduction of glucose and by maintaining the basal production rate thereafter.
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PMID:Effect of glucagon on glucose production during insulin deficiency in the dog. 69 Jan 90

Previous findings that 2.5 mM quinolinic acid inhibits gluconeogenesis more strongly from alanine than from lactate have been confirmed. 15 mM quinolinic acid completely inhibited gluconeogenesis from lactate as well as from alanine whereas the formation of glucose from fructose and the production of urea from ammonia and lactose were not affected. The pattern of the gluconeogenic intermediates was the same in the presence of 15 mM quinolinic acid as with 2.5 mM of the inhibitor. It is concluded that high as well as low concentrations of quinolinic acid inhibit gluconeogenesis at the step between oxaloacetate and phosphoenolpyruvate. Furthermore, 5-methoxyindole-2-carboxylic acid, an inhibitor of mitochondrial pyruvate metabolism, also completely blocked gluconeogenesis from lactate whereas glycerol conversion to glucose was only weakly inhibited. All these results do not support the concept of an alternate pathway of gluconeogenesis from lactate proposed by others. 2.5 mM quinolinic acid also partially blocked the formation of urea from alanine. It is suggested that quinolinic acid may have a second site of action causing an inhibition of the glutamate-pyruvate transamination owing to lack of 2-oxoglutarate in the cytosol. In the presence of quinolinic acid, glucagon caused about the same increase in aspartate and malate tissue levels in the absence of added substrates as in the presence of added lactate or alanine. Therefore, no additional effect of glucagon on gluconeogenesis from lactate or alanine prior to the block by quinolinic acid could be demonstrated.
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PMID:Effects of quinolinic acid and glucagon on gluconeogenesis in the perfused rat liver. 69 6

Blood glucose, plasma nonesterified fatty acids, amino acids, immunoreactive insulin, growth hormone, and immunoreactive glucagon responses to intravenous glucose were determined in 16 children on regular hemodialysis for chronic renal failure and nine healthy children. In the patients the fractional disappearance rate of glucose was significantly reduced, basal immunoreactive insulin was significantly raised, and while the early immunoreactive insulin response to glucose was similar in patients and controls, the late response was increased. Basal growth hormone was elevated in the patients and rose paradoxically following glucose. Fasting immunoreactive glucagon was significantly higher in the patients and was not suppressed by glucose. Plasma nonesterified fatty acid levels were lower in the patients and fell more markedly after glucose. Alanine levels, which were significantly raised in those with poor glucose tolerance, fell to normal after glucose and did not vary in those with more normal glucose tolerance. It is speculated that the metabolic and hormonal alterations may be interrelated and result from failure of normal glucose utilization.
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PMID:Hormonal and metabolic responses to intravenous glucose in children on regular hemodialysis. 70 40

Pyruvate (glyoxylate) aminotransferase from rat liver peroxisomes was highly purified and characterized. The enzyme preparation has a mol.wt. of approx. 80,000 with two identical subunits, and isoelectric point of 8.0 and a pH optimum between 8.0 and 8.5. The enzyme catalysed transamination between a number of L-amino acids and pyruvate or glyoxylate. The effective amino acceptors were pyruvate, phenylpyruvate and glyoxylate with serine, and glyoxylate and phenylpyruvate with alanine as amino donor. These properties and kinetic parameters of the enzyme are remarkably similar to those previously described for mitochondrial alanine-glyoxylate aminotransferase isoenzyme 1 from glucagon-injected rat liver [Noguchi, Okuno, Takada, Minatogawa, Okai & Kido (1978, Biochem. J. 169, 113-122].
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PMID:Purification and properties of peroxisomal pyruvate (glyoxylate) aminotransferase from rat liver. 74 24

The effects of I.V. hydrocortisone (H) (10 mg/kg) on glucose homeostasis were evaluated at 25 to 85 hours of age in 14 infants who were small for gestational age (SGA) in comparison to 17 control SGA infants. Three hours after H administration, higher levels of plasma glucose than in controls were detected (mean +/- S.E.M.): 4.78 +/- 0.2 vs. 2.88 +/- 0.2 mmol/l (p less than 0.01), while lower levels were found for blood pyruvate (38 +/- 7 vs. 89 +/- 12 mumol/l--p less than 0.01), plasma insulin (6.4 +/- 0.5 vs. 12 +/- 0.8 muIU/ml--p less than 0.05) and plasma glucagon (62.25 +/- 6.6 vs. 81.6 +/- 6.6 pmol/l--p less than 0.05). Three hours after H administration, I.V. injection of L-alanine (150 mg/kg) produced a significant rise over baseline of plasma glucose concentration from 4.78 +/- 0.2 to 5.94 +/- 0.2 mmol/l at 50 min (p less than 0.05), whereas no significant change was observed in controls. There was no significant change in plasma glucagon and insulin concentrations after L-alanine injection in either group. These results show that in SGA infants primed with H, the rise of plasma glucose concentration after L-alanine administration is observed with low plasma insulin levels and without stimulation of glucagon secretion. They suggest that H induced a reduced peripheral utilization of glucose by lowering the plasma levels of insulin and a production of glucose from alanine through gluconeogenesis.
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PMID:Effect of intravenous hydrocortisone administration on glucose homeostasis in small for gestational age infants. 75 22

Spontaneous and alanine-stimulated glucagon secretion, and its relation to plasma glucose concentration was investigated in two groups of infants during the initial two hours of life. At birth, plasma glucagon and glucose concentrations were not significantly different in healthy term newborn infants (control subjects) and infants born to insulin-dependent diabetic mothers(IDM-l). In control infants during the first hour of life, glucose fell by 43 +/- 16 mg per deciliter (mean +/- S.E.M.) while plasma glucagon rose by 44 +/- 16 pg. per milliliter (p less than 0.05 for both). However, in IDM-I despite a fall in glucose greater than in control infants, plasma glucagon failed to significantly increase. Intravenous alanine, 150 mg. per kilogram, given at one hour of life, elicited significant increments in glucose and glucagon which were positively correlated in control infants. No significant change in glucose or glucagon occurred in the diabetic group. None of the control infants developed symptomatic or biochemical hypoglycemia (plasma glucose less than 20 mg. per deciliter) whereas five of ten IDM-I developed hypoglycemia. These results suggest that spontaneous and alanine-stimulated glucagon secretion is obtunded in IDM and that this may contribute to hypoglycemia in these infants.
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PMID:Blunting of spontaneous and alanine-stimulated glucagon secretion in newborn infants of diabetic mothers. 76 May 35


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