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)

Binding sites for human GH (hGH) were studied in liver membranes of rats with chronic renal insufficiency (CRI) associated with marked growth retardation. A subtotal nephrectomy was performed in young female rats. One month after the nephrectomy, the animals with a plasma creatinine level 3 times or more that of controls were studied; their mean statural gain was 56% that of controls. The specific binding of [125I]hGH to microsomal membranes of rats with CRI was low (40% that of controls). The number of binding sites rather than the affinity of the binding was affected; both the lactogenic and somatotropic sites were decreased, as judged from the binding of ovine [125I]PRL and bovine [125I]GH. The binding sites of the plasma membranes as well as those of the Golgi fractions, were reduced. In plasma membranes of rats with CRI, the specific binding of glucagon was low, and the specific binding of insulin was elevated; these modifications were associated with a high plasma glucagon level and a decreased insulinemia in rats with CRI, but no modification of plasma GH and PRL levels was found. Thus, the hormone level does not appear to regulate the GH-binding sites in this system. The link between the growth defect and the decreased number of GH-binding sites in the liver membranes of rats with CRI remains to be established.
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PMID:Lactogenic and somatotropic binding sites in liver membranes of rats with renal insufficiency. 624 58

The characteristics and kinetics of calcium uptake activity were studied in isolated hepatic microsomes. The sustained accumulation of calcium was ATP- and oxalate-dependent. Glucagon increased microsomal Ca2+ uptake upon either in vivo injection, or in vitro perfusion of the hormone in the liver. In contrast, the effect of insulin depended on the route of administration. Calcium accumulation by subsequently isolated hepatic microsomes increased when insulin was injected intraperitoneally whereas it decreased when the hormone was perfused directly into the liver. These effects of glucagon and insulin were dose dependent. When insulin was added to the perfusate prior to the addition of glucagon, insulin blocked the glucagon-stimulated increase in microsomal Ca2+ uptake. Cyclic AMP mimicked the effect of glucagon on microsomal Ca2+ accumulation when the cyclic nucleotide was perfused into the liver. The effects of glucagon and insulin on the kinetics of hepatic microsomal Ca2+ uptake were investigated. In microsomes isolated from perfused rat livers treated with glucagon the V of the uptake was significantly increased over the control values (12.2 vs. 8.6 nmol Ca2+ per min per mg protein, P less than 0.02). In contrast, the addition of insulin to the perfusate significantly decreased the V of Ca2+ uptake by subsequently isolated microsomes (6.8 vs. 8.3 nmol Ca2+ per min per mg protein, P less than 0.05). However, neither hormone had an effect on the apparent Km for Ca2+ (4.1 +/- 0.5 microM) of the reaction. The effect of these hormones on the activity of Ca2+-stimulated ATPase was also studied. No significant changes in either V or Km for Ca2+ of the enzymatic reaction were detected.
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PMID:Characterization of the hormone-sensitive Ca2+ uptake activity of the hepatic endoplasmic reticulum. 624 28

Isolated rat hepatocytes were used to investigate the possibility of a short-term effect of glucagon on the synthesis of triacylglycerols in the liver. Incubation of hepatocytes in the presence of glucagon, followed by homogenization in a buffer containing F- (50 mM) and EDTA (2.5 mM), resulted in a 53% decrease in activity of microsomal diacylglycerol acyltransferase (EC 2.3.1.20), the only enzyme that is exclusively involved in the synthesis of triacylglycerols. The activity of cholinephosphotransferase (EC 2.7.8.2), which also uses diacylglycerols as substrate, was not decreased after exposure of the hepatocytes to glucagon. This may imply that triacylglycerol synthesis can be regulated independently of phosphatidylcholine synthesis. The activity of diacylglycerol acyltransferase in microsomes isolated from a homogenate of whole liver could be reduced by preincubating the microsomes with Mg2+ (5 mM), ATP (1 mM) and 105 000 X g supernatant. The enzyme could be reactivated by incubation of the washed microsomes with a 105 000 X g supernatant in the presence of dithiothreitol (5 mM). Fluoride (50 mM) inhibited this reactivation. It is concluded that the activity of diacylglycerol acyltransferase is subject to hormonal short-term control, possibly via a phosphorylation-dephosphorylation mechanism.
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PMID:Regulation of triacylglycerol synthesis in the liver: a decrease in diacylglycerol acyltransferase activity after treatment of isolated rat hepatocytes with glucagon. 626 42

A marked resistance to the stimulatory action of insulin on glucose metabolism has previously been shown in guinea pig, compared to rat, adipose tissue and isolated adipocytes. The mechanism of insulin resistance in isolated guinea pig adipocytes has, therefore, been examined by measuring 125I-insulin binding, the stimulatory effect of insulin on 3-0-methylglucose transport and on lipogenesis from [3-3H]glucose, the inhibitory effect of insulin on glucagon-stimulated glycerol release, and the translocation of glucose transporters in response to insulin. The translocation of glucose transporters was assessed by measuring the distribution of specific D-glucose-inhibitable [3H]cytochalasin B binding sites among the plasma, and high and low density microsomal membrane fractions prepared by differential centrifugation from basal and insulin-stimulated cells. At a glucose concentration (0.5 mM) where transport is thought to be rate-limiting for metabolism, insulin stimulates lipogenesis from 30 to 80 fmol/cell/90 min in guinea pig cells and from 25 to 380 fmol/cell/90 min in rat cells with half-maximal effects at approximately 100 pM in both cell types. Insulin similarly stimulates 3-O-methylglucose transport from 0.40 to 0.70 fmol/cell/min and from 0.24 to 3.60 fmol/cell/min in guinea pig and rat fat cells, respectively. Nevertheless, guinea pig cells bind more insulin per cell than rat cells, and insulin fully inhibits glucagon-stimulated glycerol release. In addition, the differences between guinea pig and rat cells in the stimulatory effect of insulin on lipogenesis and 3-O-methylglucose transport cannot be explained by the greater cell size of the former compared to the latter (0.18 and 0.09 micrograms of lipid/cell, respectively). However, the number of glucose transporters in the low density microsomal membrane fraction prepared from basal guinea pig cells is markedly reduced compared to that from rat fat cells (12 and 70 pmol/mg of membrane protein, respectively) and the translocation of intracellular glucose transporters to the plasma membrane fraction in response to insulin is correspondingly reduced. These results suggest that guinea pig adipocytes are markedly resistant to the stimulatory action of insulin on glucose transport and that this resistance is the consequence of a relative depletion in the number of intracellular glucose transporters.
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PMID:Proposed mechanism of insulin-resistant glucose transport in the isolated guinea pig adipocyte. Small intracellular pool of glucose transporters. 634 23

The case of a female patient with fasting hypoglycaemia before the development of Type 1 (insulin-dependent) diabetes mellitus is reported. She presented with primary hypothyroidism, partial hypopituitarism, adrenal insufficiency and glucagon deficiency. Thyroid microsomal and gastric parietal cell antibodies were detected as well as HLA-B8, whereas islet cell antibodies were not demonstrable, even 2 years after the onset of diabetes. Plasma chromatography revealed true pancreatic glucagon (IRG3500) close to undetectable in basal samples with a questionable increase from 3 to 18 pg/ml during insulin-induced hypoglycaemia. After an overnight fast, moderate hyperaminoacidaemia was found with elevations of alanine, glycine, serine, arginine and ornithine as seen in pancreatectomized patients. It is suggested that the deficient glucagon secretion in this patient might, at least in part, have been the cause of fasting hypoglycaemia and the failure of glucose recovery following insulin-induced hypoglycaemia. Possible, the A cell deficiency was part of the polyglandular failure syndrome in this patient.
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PMID:Glucagon deficiency associated with hypoglycaemia and the absence of islet cell antibodies in the polyglandular failure syndrome before the onset of insulin-dependent diabetes mellitus: a case report. 635 16

In an attempt to improve liver function and promote hepatic regeneration in a patient with severe liver injury, insulin alone or insulin and glucagon were administered by constant peripheral venous infusion during a 61-day period. The response, as assessed by a broad spectrum of hepato-cellular function tests, including synthetic, detoxification, bile metabolism, and microsomal enzyme function, and also histological evidence, indicated a beneficial effect. Continuous insulin and glucagon infusion merits further evaluation in the treatment of some forms of hepatic failure.
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PMID:Insulin and glucagon infusion in the treatment of liver failure. 638

Streptozotocin-induced diabetes produced a significant rise in rat serum and liver triacylglycerol content and hepatic triacylglycerol biosynthesis measured in vivo. Microsomes, isolated from the livers of streptozotocin-exposed animals (2-72h), exhibited an increased capacity to incorporate sn-[1,3-(14)C]glycerol 3-phosphate into neutral lipid (diacylglycerol and triacylglycerol) in the presence of ATP, CoA and palmitate. The streptozotocin-induced elevation of microsomal neutral lipid production was accompanied by a corresponding rise in the activity of microsomal phosphatidate phosphohydrolase (4-fold after 72 h of streptozotocin exposure). Diabetic-dependent increases in acylglycerol formation, phosphatidate phosphohydrolase activity and serum triacylglycerol and fatty acid levels were reversed by administering insulin (10 units protamine zinc/kg) at 16-h intervals (three separate doses( beginning 24 h after streptozotocin exposure. However, the diabetic-related rise in hepatic triacylglycerol content was only partially corrected by insulin administration. Streptozotocin-relate increases in liver triacylglycerol biosynthesis and phosphatidate phosphohydrolase activity we associated with alterations in plasma factors, since homogenates of hepatocyte monolayers exposed (18h) to plasma isolated from diabetic (72 h exposure to streptozotocin) animals exhibit an increased capacity to incorporate sn-[1,3-(14)C]glycerol 3-phosphate into triacylglycerol compared to homogenates of cells exposed to plasma from control (non-fasted) animals. The importance of these plasma factors in altering hepatic acylglycerol formation was also supported by the observation that hepatocyte monolayers exposed to a mixture of plasma isolated from normal (non-fasted) animals and plasma components elevated in diabetes (glucagon, glucose, oleate and ketones) showed increases in triacylglycerol formation which were similar to those produced by exposure to diabetic plasma. Additional studies demonstrated that fatty acids (oleate) appeared to be the agent primarily responsible for the diabetic plasma-induced rise in monolayer triacylglycerol biosynthesis and phosphatidate phosphohydrolase activity.
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PMID:The acute effects of streptozotocin-induced diabetes on rat liver glycerolipid biosynthesis. 645

The subcellular localization of glucagon-like materials in the thalamus-hypothalamus and brain stem of the rat was investigated. Both glucagon immunoreactivity (GI) determined by C-terminal specific antibody and glucagon-like immunoreactivity (GLI) determined by non-specific antibody were enriched in the microsomal and synaptosomal fractions relative to the nuclear, myelin and mitochondrial fractions. Furthermore, the synaptosomal fraction of both the thalamus-hypothalamus and brain stem incubated in Krebs-Ringer bicarbonate buffer with 55 mM K+ at 37 degrees C released GI and GLI in the presence of Ca++. These findings suggested that glucagon-like substances detected in the brain have a role in the synaptic function.
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PMID:Synaptosomal localization and release of glucagon-like materials in the rat brain. 654 65

In previous investigations, we found high rates of cholesterol synthesis in human fetal liver tissue, second only to rates in fetal adrenal tissue. Previous estimates of the amount of cholesterol in the fetus derived from the maternal compartment are in the range of 20%. Thus, the liver may be the principal source of circulating lipoproteins in the human fetus, as is true in the human adult. Low density lipoprotein is the major source of cholesterol used for fetal adrenal steroidogenesis; therefore, it follows that factors regulating cholesterol synthesis in the human fetal liver may indirectly control the rate of steroid secretion by the adrenal cortex. The purpose of the present investigation was to determine if hormones, particularly those produced by the fetal-placental unit, might serve to stimulate cholesterol synthesis in the human fetal liver. The rate of cholesterol biosynthesis was determined by measuring the rate of incorporation of [3H]water into [3H]cholesterol in hepatocytes maintained in culture or by determination of the specific activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in microsomal preparations from human fetal liver. The addition of dexamethasone (10(-10) - 10(-6)M) stimulated cholesterol synthesis up to 2- to 4-fold between days 2 and 6 of exposure. When human fetal liver cells were maintained in the presence of dexamethasone (10(-7)M), the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in microsomal fractions was stimulated 4-fold compared to that in control cells. Cortisol also stimulated cholesterol biosynthesis in a concentration-dependent manner. The addition of 17 beta-estradiol (E2) to the culture medium resulted in stimulation of cholesterol biosynthesis in a concentration-dependent manner from 10(-10) - 10(-7)M. The rate of cholesterol synthesis when E2 was present (10(-7)M) was 4-fold greater than that in untreated cells. Stimulation of cholesterol synthesis by E2 was maintained between 2-7 days of incubation with E2. Estrone, estriol, and E2 (10(-6)M) caused similar increases (3- to 4-fold) in the rates of cholesterol synthesis in human fetal hepatocytes. Finally, progesterone in concentrations greater than 10(-6) M significantly stimulated cholesterol synthesis in human fetal liver cells. In contrast, other hormones and factors, including insulin, glucagon, PRL, GH, dehydroepiandrosterone and its sulfate, epidermal growth factor, fibroblast growth factor, T3, (Bu)2cAMP, and cholera toxin, had no effect on the rate of cholesterol synthesis in human fetal liver cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cholesterol synthesis by human fetal hepatocytes: effects of hormones. 672 9

1. The effects of glucagon, insulin and phenylephrine on the phosphorylation of cytoplasmic, mitochondrial and membrane proteins were studied in intact hepatocytes from 24 h-starved rats incubated with [32P]Pi. A rapid cell-fractionation technique was used, followed by radioautography of the proteins separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 2. Glucagon consistently caused a significant increase in the phosphorylation of four readily separable cytoplasmic phosphoproteins, of Mr 93000, 50000, 46000 and 20000, and a decrease in phosphorylation of a phosphoprotein of Mr 22000. Phosphorylation of the protein of Mr 46000 was also enhanced by both phenylephrine and insulin, and that of Mr 93000 by phenylephrine. 3. The phosphoprotein of Mr 22000 was not precipitated by boiling for 5 min, and had a mobility identical with that of similar protein whose phosphorylation is enhanced in the adipocyte by insulin [Belsham & Denton (1980) Biochem. Soc. Trans. 8, 382-383]. 4. Glucagon, but not phenylephrine or insulin, enhanced the phosphorylation of a mitochondrial protein of Mr 35000 and of four plasma- or microsomal-membrane proteins of Mr 50000, 30000, 23000 and 19000. 5. Mitochondria from glucagon-treated animals or hepatocytes phosphorylated a protein of Mr 30000 when incubated in vitro with [32P]Pi and ADP. Phosphorylation of this protein did not occur with mitochondria from control, phenylephrine- or insulin-treated cells. 6. The significance of these hormonally induced changes in protein phosphorylation is discussed.
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PMID:The effects of glucagon, phenylephrine and insulin on the phosphorylation of cytoplasmic, mitochondrial and membrane-bound proteins of intact liver cells from starved rats. 676 Aug 56


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