Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Chlorothiazide twice a day plus atenolol, metoprolol, pindolol and propranolol in single daily doses administered to patients with essential hypertension achieved effective control of blood pressure. 2. Each beta-adrenoreceptor-blocking drug was associated with small, but significant, increases in plasma triglyceride concentrations and suppression of fasting immuno-reactive glucagon concentrations.
Clin Sci Mol Med Suppl 1978 Dec
PMID:beta-Adrenoreceptor-blocking agents and lipid metabolism. 3 7

Drug-induced porphyrin accumulation occurs in chick embryo liver cells maintained in serum-free Waymouth MD 705/1 medium. Addition of insulin and thyroxine to the medium results in a marked enhancement of porphyrin accumulation. The addition of hydrocortisone results in a further enhancement of porphyrine accumulation. Several agents which are reported to increase intracellular adenosine 3':5'-monophosphate (cAMP) levels, viz. glucagon, sodium fluoride, cAMP or its dibutyryl derivative, 3-isobutyl-1-methylxanthine and papaverine enhanced drug-induced porphyrin biosynthesis. On the other have, agents which are reported to decrease intra-cellular cAMP levels, viz. alloxan and imidazole, diminished drug-induced porphyrin accumulation. cAMP appears to enhance, but not to function as a "second messenger" in drug-induced porphyrin biosynthesis. Drug-induced porphyrin accumulation in chick embryo liver cells depend upon the insulin to glucagon ratio. A low level of porphyrin accumulation occurs at insulin to glucagon ratios similar to those found following glucose administration in vivo, suggesting a possible explanation for the therapeutic effect of glucose in hepatic porphyria. The 5 alpha A(A:B trans) and 5 beta H(A:Bcis) steroids are equipotent in inducing delta-aminolevulinic acid synthetase and porphyrin accumulation in chick embryo liver cells maintained in serum-free culture medium. Thus, there is no specific steric requirement for porphyrin-inducing activity in steroids.
Mol Cell Biochem 1979 May 21
PMID:Hormonal effects on the regulation of hepatic heme biosynthesis. 8 65

1. The plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) response to intravenously administered glucagon has been studied in nine hyperthyroid, five hypothyroid and ten euthyroid patients. 2. Concentrations of the nucleotide rose to a peak at 15 min and declined to near basal values by 120 min, the response being greatest in hyperthyroid and least in hypothyroid subjects. The mean peak concentrations were 1028 nmol/1 in the hyperthyroid group, 252 nmol/1 in the hypothyroid group and 534 nmol/1 in the euthyroid group. 3. These results could not be accounted for by differences in serum insulin response. 4. It is suggested that the response of plasma cyclic AMP to glucagon may serve as an index of tissue thyroid status.
Clin Sci Mol Med 1975 Jan
PMID:Plasma adenosine 3':5'-cyclic monophosphate response to glucagon in thyroid disease. 16 65

1. Glucokinase is one of four glucose phosphorylating enzymes present in rat liver. Its distinctive features are a high K-m for glucose (high-K-m isozyme) and a rather narrow substrate specificity. In contrast, the other three enzymes, collectively called hexokinases or low-K-m isozymes, exhibit low K-m values for glucose and a wider substrate specificity. 2. Glucokinase is present in the liver os mammals (with some exceptions), amphibians and lower reptiles; It is absent from higher reptiles and birds. The presence or absence of glucokinase may represent an evolutionary adaptation to feeding habits and other physiological peculiarities. Differences in the immunological behavior and in the kinetic parameters of glucokinases from different taxa suggest the operation of divergent evolution. 3. The levels of glucokinase in rat liver depend strictly on the supply of carbohydrate in the diet. Glycogen phosphorylase and glycogen synthetase behave similarly, whereas other carbohydrate-metabolizing enzymes depend on the provision of either protein or protein plus carbohydrate. Glucokinase decays with a half-life of 33 hr when rats are starved or fed a carbohydrate-free diet, and is induced by the administration of glucose. The adaptive character is not exhibited by all mammals, indicating evolutionary discrimination within the same class and even within the same single order Rodentia. Enzyme adaptation in the liver may partially explain the condition known as 'hunger diabetes'. 4. The endocrine system plays a paramount role in glucokinase adaptation, since insulin is essential for glucose-dependent glucokinase induction and, on the other hand, glucagon, catecholamines and cyclic AMP prevent the induction. Glucocorticoids and some pituitary hormones modulate the rate of induction. The mechanisms underlying the hormonal regulation of glucokinase levels are not well known. 5. The variations in liver glucokinase correspond to changes in the amount of enzyme protein as assessed by immunochemical titration. This fact agrees with the effects of inhibitors of protein synthesis on glucokinase induction. 6. An antiserum against rat glucokinase reacts with the enzyme from mammals and turtles but not with the amphibian enzyme. It does not react with low-K-m hexokinases from different sources. 7. The saturation function for glucose is sigmoidal in mammalian and amphibian glucokinases but not in glucokinase from lower reptiles. The Hill's coefficient is very constant with values about 1.6. The K0.5 (concentration for half saturation) values in the different species studied vary between 1.5 and 8 mM. These kinetic parameters may be considered as another adaptive feature aimed to give maximal efficiency to the liver uptake of glucose at the changeable concentrations in the blood resulting from variations in the amount of dietary glucose.
Mol Cell Biochem 1975 Feb 28
PMID:Adaptive character of liver glucokinase. 16 20

Thr relevance of the crystal structure of the polypeptide hormones, insulin, glucagon and human placental lactogen to conformation and flexibility in solution and to receptor binding is considered. X-ray studies for crystal forms of glucagon, human placental lactogen and three insulin derivatives (A1 acetyl insulin, A1-t-butoxy carbonyl insulin and A1 2,2-dimethyl-3-formyl-L-thiazolidine-4-carbonyl insulin) are reported. Neither glucagon nor human placental lactogen are as ordered as insulin in the crystal form. Glucagon crystals undergo distinct transformations on changing the pH of the mother liquor from pH 9.5 to pH 6, indicating that the glucagon molecule is flexible in the crystal, as it is in solution. On the other hand all insulin analogues have a similar three dimensional structure to that of native insulin. Three dimensional difference Fourier studies of two insulin derivatives at 3 A resolution indicate the position of the modifying groups and define the small conformational changes which have occurred. The in vitro biological activity and receptor binding decrease with the increasing size of the group added to A1. The correlation of the structure analysis with the biological data strongly implicate a region close to A1 in receptor binding. Insulin appears to bind to the receptor in a specific conformation similar to that observed in the crystal structure and in solution; amino acid residues which are separated in the primary structure but brought into close juxtaposition in the tertiary structure are important for full potency.
Mol Cell Biochem 1975 Jul 31
PMID:The relation of polypeptide hormone structure and flexibility to receptor binding: the relevance of X-ray studies on insulins, glucagon and human placental lactogen. 17 May 5

1. The action of insulin on plasma cyclic nucleotide concentrations in normal human subjects has been studied after intravenous injection, alone and in combination with glucagon. 2. After injection of insulin alone there was an initial small, though not significant, decrease in plasma cyclic AMP at 15 min followed by an increase to more than twice the initial concentration at 30 min. The increase was absent when hypoglycaemia was lessened by infusion of glucose after insulin injection. 3. Injection of insulin caused no significant change in plasma cyclic GMP concentration, whether or not glucose was infused after the hormone. 4. Glucagon (3-300 nmol, 10-1000 mug), caused a dose-dependent increase in plasma cyclic AMP concentration. The rise in plasma cyclic AMP produced by 3 or 30 nmol of glucagon was not significantly modified by simultaneous injection of insulin (44 nmol; 6 units).
Clin Sci Mol Med 1976 Jun
PMID:The effect of insulin on adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate concentrations in human plasma. 17 51

Fat cells were preincubated for 2 h in the presence and absence of growth hormone (GH) and Dexamethasone (Dex) before the addition of increasing concentrations of either epinephrine, theophylline or glucagon and final incubation of the cells for an additional 5 minutes. GH and Dex increased by 85%, 28% and 72%, respectively, the cAMP levels reached in the sole presence of 10(-5)M epinephrine, 10(-2)M theophylline or 5 X 10(-5)M glucagon. An adenylate cyclase particulate preparation shows that epinephrine decreases Km from 2mM to 0.6 MM and increases Vmax and the strength of interaction value (n) from 0.91 to 1.75.
Mol Cell Biochem 1976 Dec 10
PMID:Hormonal control of fat cells adenylate cyclase. 18 30

Several characteristics of the binding of insulin and glucagon to human circulating mononuclear leukocytes have been studied. Functional analysis (latex bead ingestion) revealed that cell mixtures, as prepared according to Boyum and used generally in studies of insulin resistance in humans, consist of 20-29% phagocytic monocytes, with the remainder being lymphocytes. Partial separation of monocytes from lymphocytes on columns of Sephadex G-10, followed by correlation of insulin binding with cell type, confirms that the monocyte is the binding species. Insulin influenced neither glucose uptake nor the further conversion of glucose to lipids and CO2 by the leukocytes. The transport of alpha-aminoisobutyrate, a nonmetabolizable amino acid, into these cells was also unaffected by insulin. Monocyte/lymphocyte mixtures specifically bound glucagon and prostaglandin E1. At physiological concentrations of these hormones, steady states were reached in 15 min and 45 min, respectively. In contrast to the 8-10-fold increases in cellular cyclic AMP produced by prostaglandins, the effect of glucagon was very small but apparently real. Under appropriate preincubation conditions, sodium azide and iodoacetamide inhibited phagocytosis and insulin binding in parallel. The binding of glucagon was unaffected by these agents. Although both antimycin A and actinomycin D inhibited phagocytosis of the monocytes, only the former inhibited insulin binding; there was only a slight effect on glucagon binding. We would conclude that the binding of insulin to human circulating monocytes, although reflective of insulin resistance in diabetes mellitus and obesity, may not be to traditional receptors. In contrast, the binding of glucagon to lymphocyte/monocyte mixtures may be to function-linked receptors.
Mol Cell Endocrinol 1977 Oct
PMID:Hormone receptors: VI. On the nature of the binding of glucagon and insulin to human circulating mononuclear leukocytes. 20 May 11

The splanchnic-hepatic metabolism of glucose, lactate, pyruvate, alanine, glycerol, non-esterified fatty acids (NEFA), ketone bodies and oxygen were investigated in five normal men and six juvenile diabetic subjects at rest and during exercise after an overnight fast. A linear relationship was found between load (arterial concentration multiplied by hepatic blood flow) and splanchnic-hepatic uptake of lactate, pyruvate, glycerol and NEFA. The uptake of alanine was highly sensitive to load, but was also regulated by the concentration of hepatic venous glucagon. The uptake of pyruvate was high in exercising diabetic subjects, who had a high lactate/pyruvate concentration ratio in hepatic venous blood. The rate of uptake of the total measured gluconeogenic precursors was significantly higher in the diabetic group at a given load. The rate of ketogenesis was linearly related to the NEFA load in both groups; however, the rate of ketogenesis was twofold at a given load in the diabetic group. The highest rates of ketogenesis were found coincident with the highest concentrations of glucagon in hepatic venous blood. The observed antiketogenic effect of exercise was due to a decreased load of NEFA, mainly caused by a decrease in the hepatic blood flow.
Clin Sci Mol Med 1977 Nov
PMID:Regulation of gluconeogenesis and ketogenesis during rest and exercise in diabetic subjects and normal men. 20 21

The rapid isolation of high yields of parenchymal cells from chicken liver is described. Stringent tests of viability show that the isolated hepatocytes are both structurally and metabolically similar to those in intact liver. During incubation viability decreased and the significance of this change on the interpretation of metabolic experiments is discussed. Lactate was a much more effective gluconeogenic precursor than pyruvate even in the presence of additional reducing equivalents. Hepatocytes isolated from fed chickens produced glucose from glycogen degradation. Glycogenolysis was stimulated by glucagon, dibutyryl cyclic AMP and adrenaline. Half maximal glucagon effects were elicited by physiological concentrations of the hormone. Glucagon and dibutyryl cyclic AMP stimulated glucagon, dibutyryl cyclic AMP and adrenaline their action was not additive to that of adrenaline.
Mol Cell Biochem 1978 Apr 11
PMID:The use of viable hepatocytes to study the hormonal control of glycogenolysis in the chicken. 20 19


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