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 studied the influence of hyperglycemia on glucose homeostasis in man by determining the effect of graded hyperglycemia on peripheral glucose uptake and systemic metabolism in the presence of basal and increased serum insulin concentrations in 10 normal men. This was achieved by the simultaneous application of forearm and clamp techniques (euglycemic and hyperglycemic) during the combined iv infusion of somatostatin, glucagon, and insulin. While mean (+/- SE) basal serum insulin levels (14 +/- 2 microU/ml) were maintained, the elevation of fasting arterial glucose concentrations (90 +/- 1 mg/dl) to 146 +/- 1 and 202 +/- 1 mg/dl (each for 120 min) increased forearm glucose uptake (FGU) only modestly from 0.06 +/- 0.01 to 0.15 +/- 0.02 and then to 0.24 +/- 0.03 mg/100 ml forearm X min, respectively. During physiological hyperinsulinemia (47 +/- 3 microU/ml), the influence of similar graded hyperglycemia on FGU was considerably enhanced. At plasma glucose concentrations of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, FGU rose to 0.33 +/- 0.05, 0.59 +/- 0.07, and 0.83 +/- 0.12 mg/100 ml forearm X min, respectively. The glucose infusion rate required to maintain the glucose clamp with basal insulin levels was 1.08 +/- 0.20 and 2.67 +/- 0.39 mg/kg X min at glucose concentrations of 146 +/- 1 and 202 +/- 1 mg/dl, respectively. During physiological hyperinsulinemia, however, the glucose infusion rate required was 4.15 +/- 0.39, 9.45 +/- 1.05, and 12.70 +/- 0.81 mg/kg X min at glucose levels of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, respectively. Lactate concentrations rose significantly during hyperglycemia, but the rise in the presence of increased insulin concentrations (from 0.72 +/- 0.06 to 1.31 +/- 0.11 mmol/liter; P less than 0.001) considerably exceeded the increment (from 0.74 +/- 0.05 to 0.92 +/- 0.03 mmol/liter) with basal insulin levels. While both FFA and glycerol concentrations were immediately reduced by euglycemic hyperinsulinemia, the fall in FFA during hyperglycemia in the presence of basal insulin levels preceded the decrease in glycerol concentrations by 45 min. Forearm oxygen consumption did not change throughout the study.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The influence of graded hyperglycemia with and without physiological hyperinsulinemia on forearm glucose uptake and other metabolic responses in man. 287 53

Five Type 1 (insulin dependent) diabetic patients with no endogenous insulin secretion and very low antiinsulin antibody levels (IBC less than 4%) were studied twice. Nocturnal plasma glucose was maintained by intravenous insulin just beyond each extreme of the normal range, either "hypoglycemic," at 2.71 +/- 0.03 mmol/L, or "hyperglycemic," 8.59 +/- 0.13 mmol/L. Glucose turnover measurements were performed before and after insulin was discontinued the following morning. The steady state plasma glucose concentration achieved during subsequent glycemic escape was significantly lower following nocturnal hypoglycemia, (16.1 +/- 0.3 v 20.2 +/- 0.03 mmol/L; P less than 0.01). The initial rate of rise of plasma glucose was identical in both groups. Free insulin levels, although significantly higher in the hypoglycemic study, before withdrawal, 24.3 +/- 6.0 v 13.3 +/- 0.8 mU/L, (P less than 0.01), fell to similarly low levels 1 hour after insulin withdrawal. Free fatty acid and total ketone concentrations were normalized during hypoglycemia, but remained elevated in the hyperglycemic group. Lactate concentrations were not different in the two studies. During glycemic escape glucose appearance rate (Ra) rose faster following hypoglycemia, but similar final rates were achieved in each group. When related to plasma glucose concentration glucose uptake (Rd) was normal following hypoglycemia and remained persistently greater than the hyperglycemic group throughout the 5 hours following insulin withdrawal. Plasma cortisol, pancreatic glucagon, and growth hormone levels were not significantly different in the two groups following withdrawal. It is suggested that the persistent normal glucose uptake, following glycemic control that has been sufficient to normalize plasma metabolites, will limit glycemic excursions caused by acute reductions in plasma-free insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Strict nocturnal diabetic control diminishes subsequent glycemic escape during acute insulin withdrawal. 351 51

The purpose of this study was to assess whether breathing high or low concentrations of O2 could affect glucose turnover during exercise in man. Ten healthy subjects performed two constant work-rate exercise tests, one when the fraction of inspired O2 (FIO2) was 0.15 and the other at the same work rate but when the FIO2 was 0.80. The work rate for each subject was chosen so that blood lactate would be elevated during hypoxia, but would be lower during hyperoxia. Glucose appearance (Ra) and disappearance (Rd) were measured using the primed, constant infusion of [3-3H]glucose. Although the work rate was the same during hypoxia and hyperoxia in each subject, hypoxic exercise was accompanied by a significantly larger rest to exercise increase in Rd (delta Rd) compared with hyperoxia by 265%. Similarly, delta Ra was greater during hypoxia than during hyperoxia by 188%. Lactate to pyruvate ratios were significantly higher during hypoxic exercise suggesting a shift in the cell redox to a more reduced state. Insulin and glucagon were not affected by the FIO2, but both epinephrine and norepinephrine were increased during hypoxic exercise, which may explain the increase in Ra. The regulation of blood glucose during exercise in vivo appears to be dependent on the availability of oxygen to the working muscle cells.
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PMID:Glucose turnover in response to exercise during high- and low-FIO2 breathing in man. 352 22

We have used control analysis to quantify the distribution of control in the gluconeogenic pathway in liver cells from starved rats. Lactate and pyruvate were used as gluconeogenic substrates. The flux control coefficients of the various enzymes in the gluconeogenic pathway were calculated from the elasticity coefficients of the enzymes towards their substrates and products and the fluxes through the different branches in the pathway. The elasticity coefficients were either calculated from gamma/Keq. ratios (where gamma is the mass-action ratio and Keq. is the equilibrium constant) and enzyme-kinetic data or measured experimentally. It is concluded that the gluconeogenic enzyme pyruvate carboxylase and the glycolytic enzyme pyruvate kinase play a central role in control of gluconeogenesis. If pyruvate kinase is inactive, gluconeogenic flux from lactate is largely controlled by pyruvate carboxylase. The low elasticity coefficient of pyruvate carboxylase towards its product oxaloacetate minimizes control by steps in the gluconeogenic pathway located after pyruvate carboxylase. This situation occurs when maximal gluconeogenic flux is required, i.e. in the presence of glucagon. In the absence of the hormone, when pyruvate kinase is active, control of gluconeogenesis is distributed among many steps, including pyruvate carboxylase, pyruvate kinase, fructose-1,6-bisphosphatase and also steps outside the classic gluconeogenic pathway such as the adenine-nucleotide translocator.
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PMID:Control of gluconeogenesis in rat liver cells. Flux control coefficients of the enzymes in the gluconeogenic pathway in the absence and presence of glucagon. 380 Aug 95

1. The rates of gluconeogenesis from most substrates tested in the perfused livers of well-fed rats were about half of those obtained in the livers of starved rats. There was no difference for glycerol. 2. A diet low in carbohydrate increased the rates of gluconeogenesis from some substrates but not from all. In general the effects of a low-carbohydrate diet on rat liver are less marked than those on rat kidney cortex. 3. Glycogen was deposited in the livers of starved rats when the perfusion medium contained about 10mm-glucose. The shedding of glucose from the glycogen stores by the well-fed liver was greatly diminished by 10mm-glucose and stopped by 13.3mm-glucose. Livers of well-fed rats that were depleted of their glycogen stores by treatment with phlorrhizin and glucagon synthesized glycogen from glucose. 4. When two gluconeogenic substrates were added to the perfusion medium additive effects occurred only when glycerol was one of the substrates. Lactate and glycerol gave more than additive effects owing to an increased rate of glucose formation from glycerol. 5. Pyruvate also accelerated the conversion of glycerol into glucose, and the accelerating effect of lactate can be attributed to a rapid formation of pyruvate from lactate. 6. Butyrate and oleate at 2mm, which alone are not gluconeogenic, increased the rate of gluconeogenesis from lactate. 7. The acceleration of gluconeogenesis from lactate by glucagon was also found when gluconeogenesis from lactate was stimulated by butyrate and oleate. This finding is not compatible with the view that the primary action of glucagon in promoting gluconeogenesis is an acceleration of lipolysis. 8. The rate of gluconeogenesis from pyruvate at 10mm was only 70% of that at 5mm. This ;inhibition' was abolished by oleate or glucagon.
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PMID:Carbohydrate metabolism of the perfused rat liver. 558 23

1. Phosphopyruvate carboxylase activity rapidly appears in the liver of prematurely delivered rats and development of activity is prevented by injection of actinomycin D just before delivery. 2. The activity is considerably decreased by puromycin and amino acid analogues and thus appears to be due to enzyme synthesis. 3. Newborn or premature animals show a transient intense phase of hypoglycaemia after delivery. 4. When the hypoglycaemic phase is prevented by glucose injection little phosphopyruvate carboxylase activity appears in the liver, but galactose, mannose and fructose, which have no effect on the blood glucose concentration, also repress enzyme development. 5. Lactate, pyruvate and glycerol injections repress the premature development of phosphopyruvate carboxylase. 6. Injections of glucagon, adrenalin and noradrenalin into the rat foetus in utero result in development of phosphopyruvate carboxylase activity. 7. These findings are discussed in relation to the mechanism of initiation of enzyme synthesis in neonatal rat liver.
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PMID:Factors affecting the premature induction of phosphopyruvate carboxylase in neonatal rat liver. 566 96

The effects of beta-1-adrenergic blockade (100 mg metoprolol) on metabolism in exercise was examined in 14 healthy males who worked for 50 min on a treadmill at 65% of their maximal exercise capacity. The tests were carried out in a double blind fashion. Glucose and lactate were determined in arterialized capillary blood, free fatty acids, glycerol, growth hormone, cortisol, glucagon, insulin, testosterone, and estradiol in serum, and adrenaline and noradrenaline in plasma. Lactate and glucose were not significantly affected by beta-1-adrenergic blockade, free fatty acids and glycerol were reduced by 50% and 30% respectively as compared with the unmedicated condition. Adrenaline and noradrenaline levels were increased by 104% and 54% respectively, growth hormone by 60%, cortisol by 72%, and glucagon by 36% when compared with the control experiments. Insulin and estradiol were unaffected, testosterone was depressed by 21% under medication. The results demonstrate that during prolonged exercise beta-1-adrenergic blockade depresses lipolysis. Energetic deficiency is prevented by counter-regulatory increases of various hormones. Consequently, from the metabolic point of view there is no indication of impairment of prolonged exercise capacity under beta-1-adrenergic blockade.
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PMID:[Catecholamines, GH, cortisol, glucagon, insulin, and sex hormones in exercise and beta 1-blockade (author's transl)]. 612 53

The metabolic responses to infusion of adrenaline (6 micrograms/min) and of noradrenaline (5 micrograms/min) for 120 minutes have each been studied in five normal males with and without concurrent somatostatin (250 micrograms/h). Adrenaline induced marked and sustained hyperglycaemia (maximal blood glucose at 75 min, 9.0 +/- 0.4 mmol/l) while noradrenaline induced only a mild and transient blood glucose rise. Blood lactate was elevated by adrenaline (2.57 +/- 0.47 mmol/l with adrenaline, 0.62 +/- 0.06 mmol/l with saline at 120 min, p less than 0.02). Pyruvate levels rose proportionately less so that the circulating lactate:pyruvate ratio was increased (16.6 +/- 1.3 with adrenaline, 11.4 +/- 0.9 with saline at 120 min, p less than 0.05). Lactate and pyruvate levels were unaffected by noradrenaline. Both catecholamines increased circulating non-esterified fatty acid (NEFA) and glycerol to peak at 30 min, while maximal 3-hydroxybutyrate concentrations were achieved at 50 min (0.26 +/- 0.07 mmol/l with adrenaline; 0.23 +/- 0.06 mmol/l with noradrenaline; 0.03 +/- 0.01 mol/l with saline, both p less than 0.05). Insulin levels were partially suppressed by noradrenaline, while a small rise in circulating insulin was observed with adrenaline which was also associated with a large rebound rise in insulin secretion on cessation of the infusion. Mild and transient hyperglucagonaemia was observed with adrenaline while stimulation of glucagon secretion was more sustained with noradrenaline. Somatostatin suppressed insulin, glucagon and growth hormone secretion and both magnified and prolonged the hyperglycaemic effect of adrenaline (maximal at 105 min, 11.3 +/- 0.5 mmol/l, p less than 0.01 versus adrenaline alone).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic effects of adrenaline and noradrenaline in man: studies with somatostatin. 614 42

1. The effectiveness of gluconeogenic precursors in hepatocytes isolated from 18 day old chick embryos is:Lactate much much greater than pyruvate greater than alanine = glutamine greater than glycerol and other amino acids. This result is qualitatively and quantitatively similar to hepatocytes isolated after hatching. 2. In the presence of endogenous glycogenolysis, conversion of [U-14C]lactate to glucose was used to estimate gluconeogenic flux and its control by hormones. 3. Glucagon failed to stimulate lactate gluconeogenesis although simultaneously increasing glycogenolysis. Insulin had no effects on gluconeogenesis.
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PMID:Gluconeogenesis in chick embryo isolated hepatocytes. 634 34

Whole-body tracer studies have documented abnormal glucose and amino acid kinetics in cancer-bearing man. Whether these abnormalities are related to systemic or local tumor effects is questioned. Forearm metabolism was examined in six patients with localized squamous cell carcinoma of the distal esophagus and six healthy normal male volunteers. Substrate arterio-venous differences and blood flow across forearm tissues were determined and substrate flux calculated. The mean forearm blood flow (ml min-1 100 ml forearm-1) was not significantly different between cancer patients (3.67 +/- 0.12) and normal subjects (2.80 +/- 0.40). The uptake of glucose (mumol min-1 100 ml forearm-1) was significantly higher in cancer patients (1.99 +/- 0.45) compared to control subjects without weight loss (0.47 +/- 0.18). Lactic acid release (mumol min-1 100 ml forearm-1) was significantly higher in cancer patients (-1.15 +/- 0.35) compared to control subjects (-0.26 +/- 0.14). There was no significant difference in the flux of individual amino acids between the groups, although the mean total nitrogen released from forearms of cancer-bearing patients was greater than that from normal controls. The arterial serum insulin level was significantly lower and the arterial plasma glucagon level significantly higher in cancer patients compared to control subjects. These data cannot be explained by weight loss alone and suggest a peripheral defect in metabolism in this group of cancer-bearing patients.
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PMID:Peripheral tissue metabolism in cancer-bearing man. 635 16


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