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)

Acetyl-CoA carboxylase activity was measured in digitonin-permeabilized rat hepatocytes by coupling the carboxylase reaction to the fatty acid synthase reaction. Using this assay the activity of acetyl-CoA carboxylase was covariant with the rate of fatty acid synthesis. Insulin and the tumor promotor phorbol myristate acetate were found to stimulate, and glucagon and noradrenaline to inhibit both cellular parameters. The stimulation of acetyl-CoA carboxylase by insulin developed slowly (15 to 30 min) whereas the phorbol myristate acetate effect developed faster (within 15 min). The inhibition of the enzyme caused by glucagon was already apparent within 1 min after hormone addition. Inhibition by noradrenaline, in the presence of propranolol, was also quite rapid and occurred within 2 min after addition of the agonist.
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PMID:Time course of hormonal effects on acetyl-CoA carboxylase as measured in digitonin-permeabilized rat hepatocytes. 257 37

Fatty acid metabolism was studied in periportal and perivenous hepatocytes isolated by the method of Chen & Katz [Biochem. J. (1988) 255, 99-104]. The rate of fatty acid synthesis and the activity of acetyl-CoA carboxylase were markedly enhanced in perivenous hepatocytes as compared with periportal cells. However, the response of these two parameters to short-term modulation by cellular effectors such as the hormones insulin and glucagon, the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate and the xenobiotics ethanol and acetaldehyde was similar in the two zones of the liver. In addition, perivenous hepatocytes showed a higher capacity of esterification of exogenous fatty acids into both cellular and very-low-density-lipoprotein lipids. Nevertheless, no difference between the two cell sub-populations seemed to exist in relation to the secretion of very-low-density lipoproteins. On the other hand, the rate of fatty acid oxidation was increased in periportal cells. This could be accounted for by a higher activity of carnitine palmitoyltransferase I and a lower sensitivity of this enzyme to inhibition by malonyl-CoA in the periportal zone. No differences were observed between periportal and perivenous hepatocytes in relation to the short-term response of fatty acid oxidation and carnitine palmitoyltransferase I activity to the cellular modulators mentioned above. In conclusion, our results show that: (i) lipogenesis is achieved at higher rates in the perivenous zone of the liver, whereas the fatty-acid-oxidative process occurs with a certain preference in the periportal area of this organ; (ii) the short-term response of the different fatty-acid-metabolizing pathways to cellular effectors is quantitatively similar in the two zones of the liver.
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PMID:Zonation of fatty acid metabolism in rat liver. 257 74

The purpose of this study was to investigate possible alterations induced by sepsis and endotoxicosis in the late phase of Ca2+-dependent signaling in rat liver. Hepatocytes isolated from septic or chronically endotoxin (ET)-treated rats were labeled with [32P]H3PO4 and stimulated with various agents. Proteins were resolved by one-dimensional polyacrylamide gel electrophoresis and autoradiographed. Vasopressin (VP)- and phenylephrine (PE)-induced responses were attenuated in both septic and ET-treated rats for cytosolic and membrane proteins compared with their respective controls. Glucagon and 12-O-myristate phorbol-13-acetate (TPA) affected only the phosphorylation of membrane proteins. Glucagon-induced changes in the phosphorylation of membrane proteins were affected by both sepsis and endotoxicosis, whereas TPA-stimulated phosphorylation was lowered only in endotoxicosis. Response to the Ca2+ ionophore A23187 was depressed in septic rats for cytosolic proteins. The phosphorylation of two cytosolic proteins, i.e., 93 and 61 kDa (previously identified as glycogen phosphorylase and pyruvate kinase, respectively), in response to VP, PE, and A23187 was severely impaired by endotoxicosis and sepsis. TPA did not affect the phosphorylation state of these two proteins. The results show that sepsis and endotoxicosis produce perturbations of the phosphorylation step in Ca2+ transmembrane signaling. Such changes can explain alterations of glycogenolysis and gluconeogenesis associated with sepsis and endotoxicosis.
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PMID:Protein phosphorylation in isolated hepatocytes of septic and endotoxemic rats. 258 48

Feed restriction and dietary 1,3-butanediol were used with lactating goats in an attempt to induce metabolic changes characteristic of bovine lactation ketosis and fatty liver. In Experiment 1, midlactation goats were fed 80, 102, or 114% of metabolizable energy requirements and 0, 50, or 100 g/d of 1,3-butanediol. Concentration of beta-hydroxybutyrate in blood plasma decreased with increasing metabolizable energy but was increased greatly at 2 h after goats were fed 50 or 100 g butanediol and remained elevated at 6 h postfeeding with 100 g of butanediol. Concentration of glucose in plasma was decreased at 2 and 6 h postfeeding in goats fed 100 g of butanediol. In Experiment 2, goats in early lactation were fed for ad libitum intake or were restricted to 70% of ad libitum intake with 1,3-butanediol included at 10% of diet DM. The treatment decreased milk production, increased concentrations of beta-hydroxybutyrate and nonesterified fatty acids, and decreased the concentration of insulin and the insulin to glucagon ratio in plasma. Concentrations of glucose, acetate, and glucagon in plasma were not affected. After 28 d of treatment, concentration of total lipid in liver was increased, but concentrations of glycogen and triglyceride were unaffected. Changes caused in goats by feed restriction plus dietary 1,3-butanediol were characteristic of subclinical lactation ketosis in cows, but the response was more moderate than seen previously in cows.
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PMID:Metabolic responses of lactating goats to feed restriction and dietary 1,3-butanediol. 262 43

We examined transthyretin immunoreactivity (TTR-IR) in human and porcine liver, choroid plexus, and pancreatic islets with both polyclonal and monoclonal antibodies to TTR. The specificity of the immunoreactions and the effects of various fixatives were tested in immunohistochemical and dot-blot systems. B-5 fixative (mercuric chloride and sodium acetate in formalin) was the best immunopreservative. In both species, the TTR-IR in choroid plexus epithelial cells was strong and was much greater than that in hepatocytes. Glucagon cells in pancreatic islets were also strongly TTR immunoreactive. Insulin cells were slightly TTR immunoreactive in human but strongly so in porcine pancreas. The finding of TTR-IR in normal islets explains the presence of TTR-IR in human endocrine pancreatic tumors, notably glucagonomas and malignant insulinomas.
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PMID:Transthyretin immunoreactivity in human and porcine liver, choroid plexus, and pancreatic islets. 264 94

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects and drug interactions, dosage, availability and cost, and indications for use of octreotide, a new synthetic analogue of the peptide hormone somatostatin (SS), are reviewed. Like SS, octreotide suppresses secretion of pituitary growth hormone (GH) and thyrotropin and decreases release of a variety of pancreatic islet cell hormones including insulin, glucagon, and vasoactive intestinal peptide (VIP). Octreotide also reduces splanchnic blood flow, gastric acid secretion, GI motility, and pancreatic exocrine function and alters the absorption of water, electrolytes, and nutrients from the GI tract. The elimination half-life of i.v. octreotide is 72-98 minutes, compared with 2-3 minutes for i.v. SS. Usual administration of octreotide is by the i.v. or s.c. route. Octreotide has been studied in the treatment of hormone-secreting pituitary tumors and pancreatic islet cell tumors. Octreotide therapy lowers GH secretion and improves clinical symptoms in patients with acromegaly and may suppress clinical symptoms to a greater degree than bromocriptine. Patients with carcinoid syndrome and VIP-secreting tumors (vipomas) have had substantial improvement in clinical symptoms with administration of octreotide. This agent does not appear to be effective in the treatment of nonvariceal upper GI bleeding and acute pancreatitis; its relative usefulness in the treatment of variceal bleeding is not established. Adverse effects associated with octreotide therapy generally have been mild, including pain or burning at the injection site, abdominal pain, and diarrhea. Octreotide has been shown to interfere with absorption of oral cyclosporine. Standard initial therapy is octreotide acetate 50-100 micrograms s.c. every 8-12 hours, with titration based on clinical and biochemical effects. Up to 3000 micrograms/day of octreotide acetate has been administered to patients with acromegaly without serious adverse effect. Octreotide is marketed under the brand name Sandostatin and is available in 1-mL ampuls containing 50, 100, and 500 micrograms of octreotide acetate. Because the conditions for which octreotide appears to be most effective are uncommon, the drug should be considered for addition to the formulary in tertiary-care institutions only; addition of octreotide to the formulary of a community hospital is probably unnecessary. The synthetic analogue octreotide is longer acting and more specific in pharmacologic action than SS.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Octreotide, a new somatostatin analogue. 265 11

Excessive hepatic glucose output is an important factor in the fasting hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM). To determine the relative contributions of gluconeogenesis and glycogenolysis in a quantitative manner, we applied a new isotopic approach, using infusions of [6-3H]glucose and [2-14C]acetate to trace overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis in 14 postabsorptive NIDDM subjects and in 9 nondiabetic volunteers of similar age and weight. Overall hepatic glucose output was increased nearly twofold in the NIDDM subjects (22.7 +/- 1.0 vs. 12.0 +/- 0.6 mumol.kg-1.min-1 in the nondiabetic volunteers, P less than .001); phosphoenolpyruvate gluconeogenesis was increased more than threefold in the NIDDM subjects (12.7 +/- 1.4 vs. 3.6 +/- 0.4 mumol.kg-1.min-1 in the nondiabetic subjects, P less than .001) and was accompanied by increased plasma lactate, alanine, and glucagon concentrations (all P less than .05). The increased phosphoenolpyruvate gluconeogenesis accounted for 89 +/- 6% of the increase in overall hepatic glucose output in the NIDDM subjects and was significantly correlated with the fasting plasma glucose concentrations (r = .67, P less than .01). Glycogenolysis, calculated as the difference between overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis, was not significantly different in the NIDDM subjects (9.9 +/- 0.06 mumol.kg-1.min-1) and the nondiabetic volunteers (8.4 +/- 0.3 mumol.kg-1.min-1). We conclude that increased gluconeogenesis is the predominant mechanism responsible for increased hepatic glucose output in NIDDM.
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PMID:Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. 265 26

The amount of glycogen that is formed by gluconeogenetic pathways during glucose loading was quantitated in human subjects. Oral glucose loading was compared with its intravenous administration. Overnight-fasted subjects received a constant infusion or [3-3H]glucose and a marker for gluconeogenesis, [U-14C]lactate or sodium [14C]bicarbonate [14C]bicarbonate). An unlabeled glucose load was then administered. Postabsorptively, or after glucose infusion was terminated, a third tracer ([6-3H]glucose) infusion was initiated along with a three-step glucagon infusion. Without correcting for background stimulation of [14C]glucose production or for dilution of 14C with citric acid cycle carbon in the oxaloacetate pool, the amount of glycogen mobilized by the glucagon infusion that was produced by gluconeogenesis during oral glucose loading was 2.9 +/- 0.7 g calculated from [U-14C]-lactate incorporation and 7.4 +/- 1.3 g calculated using [14C]bicarbonate as a gluconeogenetic marker. During intravenous glucose administration the latter measurement also yielded 7.2 +/- 1.1 g. When the two corrections above are applied, the respective quantities became 5.3 +/- 1.7 g for [U-14C]lactate as tracer and 14.7 +/- 4.3 and 13.9 +/- 3.6 g for oral and intravenous glucose with [14C]bicarbonate as tracer (P less than 0.05, vs. [14C]-lactate as tracer). When [2-14C]acetate was infused, the same amount of label was incorporated into mobilized glycogen regardless of which route of glucose administration was used. Comparison with previous data also suggests that 14CO2 is a potentially useful marker for the gluconeogenetic process in vivo.
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PMID:Hepatic glycogen in humans. II. Gluconeogenetic formation after oral and intravenous glucose. 266 12

The stimulations of ureagenesis and cyclic AMP accumulation induced by glucagon were inhibited by 10 nM vasopressin or 100 nM phorbol 12-myristate 13-acetate (PMA). The maximal accumulation of cyclic AMP induced by glucagon was clearly diminished by these agents without change in the EC50 for the peptide hormone suggesting a non-competitive type of inhibition. H-7 blocked the inhibition of glucagon-stimulated ureagenesis induced by PMA and vasopressin and diminished their effect on the accumulation of cyclic AMP induced by glucagon. It is concluded that activation of protein kinase C inhibits the stimulation of ureagenesis and the accumulation of cyclic AMP induced by glucagon in liver cells from hypothyroid rats; H-7 inhibits the effects of protein kinase C activation.
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PMID:Effect of H-7 on the modulation of glucagon actions by activators of protein kinase-C. 271 14

Glucagon was injected directly into the medial amygdala (AMYG) of rabbits, and changes in hepatic acetate metabolism were studied. The injection of 3 ng glucagon into the AMYG of intact rabbits increased the rates of 14C transfer from 14C-1-acetate into CO2, glucose, ketone bodies, cholesterol ester, free fatty acids and phospholipids but decreased those of 14C transfer into triglyceride. However, the glucagon injection into the AMYG of rabbits with lesions of stria terminals or into the parietal cortex of intact rabbits had no effects on the hepatic acetate metabolism. These observations support the hypothesis that the AMYG is a part of the glucagon-sensitive brain regulator system in the hepatic acetate metabolism.
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PMID:Influence of microinjection of glucagon into the amygdala on hepatic acetate metabolism in rabbits. 273 41


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