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 isolated hepatocyte preparation (from 24-hour fasted rats) comprised a homogeneous population of intact cells as shown by electron microscopy. Homogenates of hepatocytes were incubated for 10 minutes in an ionic buffer solution containing 1.5% gelatin with and without hormones and centrifuged at 27,500 X g for 30 minutes, and the supernatant fractions were assayed for enzyme activities. Hexokinase activity was absent, although it was easily detectable in the same fraction of intact liver. The activity of glucokinase was uninfluenced by any of the hormones. The assayable activity of fructose diphosphatase was not increased by glucagon, monobutyryl cyclic adenosine-3',5'-monophosphate (mb-cAMP), or epinephrine, nor was it inhibited by insulin. The activities of phosphofructokinase and pyruvate kinase were not increased by insulin; however, glucagon and mb-cAMP inhibited the assayable activity of phosphofructokinase and pyruvate kinase to 20 to 25% of control values. Epinephrine did not influence the assayable activity of either enzyme, although it stimulated gluconeogenesis as markedly as did glucagon and mb-cAMP. When liver cell homogenates were subjected to centrifugation at higher forces (37,400 X g for 60 minutes or greater), the assayable activity of phosphofructokinase in supernatant fractions began to diminish. Additional loss of phosphofructokinase activity was observed in supernates prepared from cells that had been incubated with epinephrine; however, in these supernatant fractions, pyruvate kinase activity did not differ from control values. The results reported here demonstrate (1) a behavior of phosphofructokinase which is not predictable on the basis of its known solubility properties, and (2) differential effects of glucagon and epinephrine on the activity of phosphofructokinase which suggest that separate mechanisms are operative in stimulation of glucoeogenesis by glucagon and epinephrine.
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PMID:Gluconeogenesis in isolated rat hepatic parenchymal cells. IX. Differential effects of glucagon and epinephrine on phosphofructokinase and pyruvate kinase. 13 35

The activities of jejunal carbohydrate-metabolizing enzymes show adaptive drugs, and sex hormones. To learn whether insulin, tolbutamide, and glucagon had effects on these enzymes, we performed serial peroral jejunal biopsies in normal young men and in obese patients, before and after treatment with these agents. Jejunal mucosa was assayed for glycolytic enzyme activities, pyruvate kinase (PK), hexokinase (HK), and fructose-1,6-diphosphate aldolase (FDPA), and the nonglycolytic enzyme activity, fructose diphosphatase (FDPase). Insulin significantly increased the activity of jejunal PK (+48% change from control) and HK (+6%), decreased the activity of FDPase (-36%),and had no effect on FDPA. Glucagon had opposite effects; the activity of PK was decreased (-33%) and FDPase was increased (+50%). Tolbutamide significantly increased the activities of PK (+47%), HK (+14%), and FDPA (+7%), and decreased the activities of FDPase (-36%). The results of tolbutamide on glycolytic enzyme activities were independent of endogenous insulin. The data support the concept that jejunal carbohydrate-metabolizing enzymes in man respond to hormones and drugs similar to responses observed in rat liver. This is important because it now gives us a means of studying the actions of these hormones directly in human tissue.
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PMID:Effects of insulin, tolbutamide, and glucagon on activities of jejunal carbohydrate-metabolizing enzymes in humans. 16 65

1. Measurements of pyruvate carboxylase, mitochondrial phosphoenolpyruvate carboxykinase (GTP), hexose bisphosphatase and glucose 6-phosphatase in developing sheep liver showed substantial activities of all enzymes in the foetus, especially towards the end of gestation. Cytosol phosphoenolpyruvate carboxykinase (GTP) in livers of mid-term foetuses was only 10% of the activity at birth. 2. All enzymes except pyruvate carboxylase showed 1.5-2-fold increases after birth. 3. Gluconeogenesis form [14C]actate could not be detected in chronically cannulated sheep foetuses at any developmental stage and was not initiated by the infusion of adrenaline or glucagon. 4. An active pathway of gluconeogenesis was evident in vivo within 2 min after natural birth or within 4 min after Caesarian delivery of term lambs, and was delayed in prematurely delivered lambs until breathing was established and the blood fully oxygenated. 5. It is proposed that oxygen availability initiates gluconeogenesis in the newborn lamb.
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PMID:The appearance of gluconeogenesis at birth in sheep. Activation of the pathway associated with blood oxygenation. 19 81

1. Glucagon stimulated gluconeogenesis from both [U-14C]lactate and [14C]xylitol in isolated perfused mouse liver. 2. Addition of cyclic AMP also stimulated gluconeogenesis from [U-14C]lactate. 3. Glucagon caused a rapid (2.5 min) 12-fold increase in hepatic cyclic AMP but not cyclic GMP concentration. 4. Glucagon caused a rapid and stable decrease in hepatic fructose 1,6-diphosphatase activity measured in vitro. 5. The results are interpreted to indicate that glucagon stimulates hepatic gluconeogenesis in mice via cyclic AMP by two different mechanisms: (a) increased substrate uptake (i.e. utilization) and (b) increased gluconeogenic efficiency (i.e. inhibition of alternate substrate fates).
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PMID:Regulation of carbohydrate metabolism in mouse liver. Effect of glucagon on gluconeogenic/glycolytic flux in isolated perfused livers. 23 88

Brook charr (Salvelinus fontinalis) were maintained at one of two stocking densities (SD) (30 or 120 kg/m3) and fed either a control or a T3-supplemented (20 mg/kg) diet for 30 days in order to investigate possible interactive effects of SD and T3-administration on growth, feeding rate, food conversion efficiency, and hepatic and dark muscle enzyme activity. In addition, liver slices were incubated in vitro for 6 h with epinephrine, norepinephrine, isoproterenol, propranolol, insulin, glucagon, or somatostatin to evaluate possible SD-T3 interactive effects on hepatic responses to hormonal stimulation. Maintaining the fish at high SD appeared to increase the clearance rate of T3 from the T3-supplemented group. There was no clear evidence of SD-T3 interactive effects on growth rate, feeding rate, or food conversion efficiency, although T3-administration decreased food conversion efficiency, and high SD decreased growth and feeding rates. Of the hepatic enzymes studied, HOAD, malic enzyme, G6PDH, CS, PFK, HK, and GDH activities all showed changes suggestive of interactive SD-T3 effects. Although hepatic FBPase was stimulated by both high SD and T3-administration, there was no evidence of interactive SD-T3 effects. Dark muscle HOAD, CS, and PFK also showed SD-T3-related responses; dark muscle malic enzyme, G6PDH, HK, and GDH were unaffected by either altered SD or T3-administration. Prior treatment of the fish with T3 and high SD had significant effects on free fatty acid (ffa) release to the medium and on hepatic lipid content, but had no effect on the responses to the various endocrine agents used. Glucose release from liver slices of fish stocked at high density (both T3-supplemented and controls) was higher than that of the fish stocked at low density; with the exception of insulin and glucagon, glucose release was similar in all pre-treatment groups. The insulin- and glucagon-stimulated changes in glucose release seen in the fish fed non-supplemented diets were not found in the two groups of fish fed the T3-supplemented diets. High SD and/or T3-administration induced significant lowering of hepatic glycogen content, but there was no effect of pre-treatment on the response to any of the endocrine agents used. The data show a marked effect of SD on energy partitioning processes in brook charr and the animal's ability to respond to T3-stimulation, but provided no evidence of such effects on the liver response to the various agents used.
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PMID:Interactive effects of high stocking density and triiodothyronine-administration on aspects of the in vivo intermediary metabolism and in vitro hepatic response to catecholamine and pancreatic hormone stimulation in brook charr, Salvelinus fontinalis. 164 21

1. The regulation of renal gluconeogenesis was studied in rats made septic by a caecal ligation and puncture technique. 2. Blood glucose concentrations were not markedly different in septic rats, but lactate, pyruvate and alanine concentrations were markedly increased, compared with sham-operated rats. Conversely, blood ketone body concentrations were significantly decreased in septic rats. Both plasma insulin and glucagon concentrations were markedly elevated in response to sepsis. 3. The maximal activities of glucose-6-phosphatase (EC 3.1.3.9), fructose-1,6-bisphosphatase (EC 3.1.3.11), pyruvate carboxylase (EC 6.4.1.1) and phosphoenolpyruvate carboxykinase (EC 4.1.1.49) were markedly decreased in kidneys obtained from septic rats, suggesting diminished renal gluconeogenesis. 4. Renal concentrations of lactate, pyruvate and other gluconeogenetic intermediates were markedly elevated in septic rats, whereas those of acetyl-CoA and fructose 2,6-bisphosphate were decreased and unchanged, respectively. 5. The rate of gluconeogenesis from added lactate, pyruvate and glycerol was decreased in isolated incubated renal tubules from septic rats. 6. Sepsis decreased the arteriovenous concentration difference for glucose, lactate, and alanine. Septic rats showed decreased net rates of glucose production and net rates of removal of lactate and alanine as compared with sham-operated controls. 7. It is concluded that the diminished capacity for renal gluconeogenesis in septic rats could be the result of changes in the maximal activities or regulation of key non-equilibrium gluconeogenic enzymes or both, but the effect of other factors (e.g. toxins) has not been excluded.
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PMID:Metabolic regulation of renal gluconeogenesis in response to sepsis in the rat. 217 16

Metabolic regulation of gluconeogenesis and glycogenolysis by two phosphorylated derivatives of glycerol, G3P, and DHAP, and by F2,6BP, was assessed in vitro in liver homogenates obtained from Chinese hamsters (C. griseus) of two types: diabetic animals from sublines with consistent glycosuria and hyperglycemia, and normoglycemic controls. Only FBPase was sensitive to inhibition by the phosphorylated metabolites. G3P was weakly inhibitory of FBPase. Addition of 7 X 10(-3) M DHAP halved FBPase activity in the diabetic hamsters and 4 X 10(-3) M DHAP produced the same effect in the controls. The other gluconeogenic enzymes and phosphorylase a were only negligibly inhibited. In contrast, F2,6BP inhibited FBPase at concentrations in the micromolar range. Liver homogenates from diabetic hamsters appeared significantly more sensitive to F2,6BP inhibition of FBPase than those from controls at concentrations 0.6 X 10(-6) M and higher. These data indicate that in well-fed hamsters phosphorylated glycerol derivatives are unlikely to regulate hepatic gluconeogenesis at physiologic concentrations. However, the effects of F2,6BP on gluconeogenesis and glycolysis may be linked to those mediated by insulin. Thus, the deficiency of insulin, elevated end-organ insulin resistance, the alteration in the glucagon-insulin interaction, or a combination of these possible causes can be involved in an abnormal regulation of glycolysis and gluconeogenesis at the FBPase step, associated with changes in F2,6BP concentration.
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PMID:Regulation of hepatic gluconeogenesis and glycogenolysis by phosphorylated glycerol and glycolytic intermediates in diabetic and control Chinese hamsters. 295 69

Plasma insulin, glucagon, glucose, free fatty acids and glycerol, hepatic cyclic AMP and glycogen, and liver phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase (FBPase), glucose 6-phosphatase (G6Pase) and alanine amino transferase (AAT) activities were examined in adult rats during the first 24 h of either starvation or consumption of a high protein, carbohydrate-free (HP) diet. Under both nutritional conditions, plasma insulin fell within 12 h and remained constant thereafter. Glucagon increased 12 h after the start of the experiment and peaked between 18-24 h. The insulin: glucagon ratio was lower during the last 12 h of the experiment. In both experimental groups, liver cyclic AMP increased progressively and peaked between 15-24 h, but it increase was higher on HP diet than on starvation. Whereas plasma glucose remained low on starvation for 24 h, it returned to normal on consumption of the HP diet. In both groups, liver glycogen fell within 12 h and remained low until the end of experiment. FBPase, G6Pase and AAT did not change on starvation, while they increased toward the end of 1 d HP consumption. During starvation or consumption of the HP diet, PEPCK increased progressively and peaked between 15-24 h, but the increase was greater with the HP diet than with starvation. These findings suggest that in the first 24 hours, the adaptative response of hepatic gluconeogenesis is higher with a HP diet than upon starvation.
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PMID:Comparison between starvation and consumption of a high protein diet: plasma insulin and glucagon and hepatic activities of gluconeogenic enzymes during the first 24 hours. 300 46

Acute hormonal regulation of liver carbohydrate metabolism mainly involves changes in the cytosolic levels of cAMP and Ca2+. Epinephrine, acting through beta 2-adrenergic receptors, and glucagon activate adenylate cyclase in the liver plasma membrane through a mechanism involving a guanine nucleotide-binding protein that is stimulatory to the enzyme. The resulting accumulation of cAMP leads to activation of cAMP-dependent protein kinase, which, in turn, phosphorylates many intracellular enzymes involved in the regulation of glycogen metabolism, gluconeogenesis, and glycolysis. These are (1) phosphorylase b kinase, which is activated and, in turn, phosphorylates and activates phosphorylase, the rate-limiting enzyme for glycogen breakdown; (2) glycogen synthase, which is inactivated and is rate-controlling for glycogen synthesis; (3) pyruvate kinase, which is inactivated and is an important regulatory enzyme for glycolysis; and (4) the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase bifunctional enzyme, phosphorylation of which leads to decreased formation of fructose 2,6-P2, which is an activator of 6-phosphofructo-1-kinase and an inhibitor of fructose 1,6-bisphosphatase, both of which are important regulatory enzymes for glycolysis and gluconeogenesis. In addition to rapid effects of glucagon and beta-adrenergic agonists to increase hepatic glucose output by stimulating glycogenolysis and gluconeogenesis and inhibiting glycogen synthesis and glycolysis, these agents produce longer-term stimulatory effects on gluconeogenesis through altered synthesis of certain enzymes of gluconeogenesis/glycolysis and amino acid metabolism. For example, P-enolpyruvate carboxykinase is induced through an effect at the level of transcription mediated by cAMP-dependent protein kinase. Tyrosine amino-transferase, serine dehydratase, tryptophan oxygenase, and glucokinase are also regulated by cAMP, in part at the level of specific messenger RNA synthesis. The sympathetic nervous system and its neurohumoral agonists epinephrine and norepinephrine also rapidly alter hepatic glycogen metabolism and gluconeogenesis acting through alpha 1-adrenergic receptors. The primary response to these agonists is the phosphodiesterase-mediated breakdown of the plasma membrane polyphosphoinositide phosphatidylinositol 4,5-P2 to inositol 1,4,5-P3 and 1,2-diacylglycerol. This involves a guanine nucleotide-binding protein that is different from those involved in the regulation of adenylate cyclase. Inositol 1,4,5-P3 acts as an intracellular messenger for Ca2+ mobilization by releasing Ca2+ from the endoplasmic reticulum.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms of hormonal regulation of hepatic glucose metabolism. 303 41

We studied the effects of insulin and glucagon on energy and carbohydrate metabolism of rat hepatocytes in primary culture. The aim of this study is to elucidate the mechanism of the synergistic action of insulin and glucagon and to evaluate the combined effects of these hormones on liver injury. Insulin increased the level of adenosine triphosphate in hepatocytes in the presence of glucagon. Insulin increased the activities of glucokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40) type L and glucose 6-phosphate dehydrogenase (EC 1.1.1.49). Glucagon had no antagonistic effect on these increases. Glucagon increased the activity of glucose 6-phosphate (EC 3.1.3.9) (G6Pase) in the presence or absence of insulin, while insulin had no effects on the levels of G6Pase and fructose 1,6-bisphosphatase (EC 3.1.3.11) in the presence or absence of glucagon. Metabolite analysis of cultured hepatocytes indicated that insulin and glucagon have antagonistic effects on the glycolytic activity of hepatocytes. These combined effects of insulin and glucagon may partially explain the preventive effects of these hormones on liver injury.
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PMID:Effects of insulin and glucagon on energy and carbohydrate metabolism of rat hepatocytes in primary culture. 306 23


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