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)

Heme oxygenase (HO), the enzyme system catalyzing the conversion of heme to bilirubin, was studied in the liver and spleen of fed, fasted, and refed rats. Fasting up to 72 hr resulted in a threefold increase in hepatic HO activity, while starvation beyond this period led to a gradual decline in enzyme activity. Refeeding of rats fasted for 48 hr depressed hepatic HO activity to basal values within 24 hr. Splenic HO was unaffected by fasting and refeeding. Hypoglycemia induced by injections of insulin or mannose was a powerful stimulator of hepatic HO. Glucose given together with the insulin abolished the stimulatory effect of the latter. Parenteral treatment with glucagon led to a twofold, and with epinephrine to a fivefold, increase of hepatic HO activity; arginine, which releases endogenous glucagon, stimulated the enzyme fivefold. These stimulatory effects of glucagon and epinephrine could be duplicated by administration of cyclic adenosine monophosphate (AMP), while thyroxine and hydroxortisone were ineffective. Nicotinic acid, which inhibits lipolysis, failed to modify the stimulatory effect of epinephrine. None of these hormones altered HO activity in the spleen. These findings demonstrate that the enzymatic mechanism involved in the formation of bilirubin from heme in the liver is stimulated by fasting, hypoglycemia, epinephrine, glucagon, and cyclic AMP. They further suggest that the enzyme stimulation produced by fasting may be mediated by glucagon released in response to hypoglycemia. The possibility is considered that the enhanced HO activity in the liver may increase hepatic heme turnover and hence, bilirubin production, which may explain the rise of unconjugated serum bilirubin observed in fasting or hypoglycemic individuals.
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PMID:Metabolic regulation of heme catabolism and bilirubin production. I. Hormonal control of hepatic heme oxygenase activity. 433 19

Catecholamines induced an increase in the activity of rat adipose tissue and liver phosphopyruvate carboxylases that was maintained for 48h. The response of adipose tissue phosphopyruvate carboxylase was blocked by actinomycin D, corticosteroids and propranolol, whereas corticosteroids and propranolol did not affect the liver enzyme. Cortisol phosphate, like actinomycin D, interfered only with the initiation of the increase in enzyme activity caused by noradrenaline, but not with the process of enzyme accumulation. In contrast, cycloheximide was effective in blocking enzyme induction throughout the course of the catecholamine effect. Adrenocorticotrophic hormone caused a short-term induction of adipose tissue phosphopyruvate carboxylase, which could be blocked by propranolol. Hepatic phosphopyruvate carboxylase, but not the adipose tissue enzyme, was induced by dibutyryladenosine 3':5'-cyclic monophosphate and by glucagon. Both nicotinic acid and nicotinamide decreased the normal induction of adipose tissue phosphopyruvate carboxylase caused by starvation, but only nicotinamide increased the activity of the liver enzyme.
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PMID:The interaction of catecholamines and adrenal corticosteroids in the induction of phosphopyruvate carboxylase in rat liver and adipose tissue. 434 97

The present investigation was undertaken to ascertain whether alterations in plasma free fatty acids (FFA) affect pancreatic glucagon secretion in man since FFA have been reported to influence pancreatic alpha cell function in other species. Elevation of plasma FFA from a mean (+/-SE) basal level of 0.478+/-0.036 mM to 0.712+/-0.055 mM after heparin administration caused plasma glucagon levels to fall approximately 50%, from a basal value of 122+/-15 pg/ml to 59+/-14 pg/ml (P < 0.001). Lowering of plasma FFA from a basal level of 0.520+/-0.046 mM to 0.252+/-0.041 mM after nicotinic acid administration raised plasma glucagon from a basal level of 113+/-18 pg/ml to 168+/-12 pg/ml (P < 0.005). Infusion of glucose elevated plasma glucose levels to the same degree that heparin raised plasma FFA levels. This resulted in suppression of plasma glucagon despite the fact that plasma FFA levels also were suppressed. Glucagon responses to arginine were diminished after elevation of plasma FFA (P < 0.01) and during infusion of glucose (P < 0.01). Diminution of plasma FFA by nicotinic acid did not augment glucagon responses to arginine. These results thus demonstrate that rather small alterations in plasma FFA within the physiologic range have a significant effect on glucagon secretion in man. Although the effects of glucose appear to predominate over those of FFA, alterations in plasma FFA may nevertheless exert an important physiologic influence over human pancreatic alpha cell function, especially in the postabsorptive state.
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PMID:Effects of alternations of plasma free fatty acid levels on pancreatic glucagon secretion in man. 482 25

The toxic effects associated with rapid lipid mobilization and a high plasma free fatty acid (FFA) concentration produced by glucagon were evaluated. Glucagon (0.5 mg/kg of body wt) was injected intravenously into nonfasting geese. The geese developed rapid respirations and high plasma FFA levels within 15 min after the glucagon injection; three of eleven died. Control geese, injected with saline, did not exhibit toxic signs. Peak FFA concentrations developed 15 min after glucagon and high levels persisted for over 90 min. Geese injected with glucagon frequently developed electrocardiographic abnormalities that included supraventricular tachycardia, premature ventricular contractions, and signs of myocardial ischemia. Light and electron microscopy revealed acute myocardial degeneration and fatty infiltration of the liver. The increase in plasma FFA concentrations and toxic effects were not prevented by pretreatment with nicotinic acid or propranolol.
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PMID:Toxic effects of glucagon-induced acute lipid mobilization in geese. 572 81

After mentioning insulin deficiency diabetes in animals produced by drugs such as Alloxan, Diazoxide or Streptozotocin only drugs are discussed, which are used in elderly patients and may either provoke diabetes mellitus (or temporary hyperglycemia) or may change the clinical course of diabetes. In the first group endocrine products such as corticosteroids, estrogens, somatotrophic hormone, thyroid hormone, glucagon, somatostatin, catecholamines and hormones with anabolic effects are listed. The second group comprises saluretics, salicylates, amphetamines, pentamidine, nicotinic acid and its derivatives, beta-receptor blockers and finally laxatives. Hypopotassemia alone can also be the cause of hyperglycemia. Speaking of the sulfonylureapreparations, their interaction with alcohol, with phenylbutazone, with some sulfonamides and the effect of the sulfonylureas on peripheric insulin-receptors is discussed. In case of severe diabetic vascular disease the use of anticoagulants may lead to hemorrhages. If such an hemorrhage occurs in the eyes, it may lead to blindness. In diabetic nephropathy the use of phenacetine and its derivatives should be substituted by another medication. This review is not at all complete but should only show some of the problems in the treatment of elderly diabetic patients.
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PMID:[Iatrogenic diabetes mellitus (side effects and interactions of drugs during clinical diabetes mellitus (author's transl)]. 612 38

Postprandial elevation of 5-phosphoribosyl 1-diphosphate (PPRibP) concentration in the mouse liver (Lalanne, M. and Henderson, J.F. (1975) Can. J. Biochem. 53,394-399) was further studied regarding the effects of protein intake and the underlying mechanisms. The extent and duration of the increase depended on the quantity and quality of proteins ingested. The order of effectiveness of various diets was as follows: 60% casein greater than 20% egg albumin greater than 20% casein greater than 20% gelatin = 20% gluten greater than 20% zein greater than 0% casein. Hepatic purine and pyrimidine biosyntheses de novo, as measured by labelled tracer incorporation, increased with increasing protein intake. Nicotinic acid incorporation into NAD increased equally, whether casein-containing or casein-free diets were given. Therefore, the increase of PPRibP level may be brought about by increase in its synthesis. Administration of glucagon or epinephrine similarly elevated the hepatic level of PPRibP. Somatostatin, known to inhibit secretion of pancreatic hormones, suppressed the casein-diet-dependent PPRibP level increase. Colchicine markedly inhibited the casein-diet- and glucagon-dependent responses, but not the epinephrine effect. It is likely that glucagon is a major factor in mediation of the protein-diet-dependent PPRibP level increase and that the cytoskeleton is involved in the glucagon-mediated response.
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PMID:Protein-diet-induced elevation of 5-phosphoribosyl 1-diphosphate concentrations in mouse liver associated with increased syntheses of various nucleotides and the possible involvement of glucagon. 620 43

Cardiostimulation produced by noradrenaline, glucagon, or tachycardia on the isolated perfused rat heart produced a metabolic coronary dilatation that was potentiated by nicotinic acid or its amide [NIC; 0.05-1.0 mM] without affecting the cardiostimulation. Reactive hyperaemia to brief coronary occlusion was unaffected by NIC, thus confirming that its vasodilator mechanism is of a different nature than that leading to metabolic coronary dilatation. It is suggested that NIC may be of significance as an adjuvant in the treatment of certain types of coronary insufficiencies.
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PMID:Enhancement of metabolic coronary vasodilatation by nicotinic acid or amide. 623 26

Two chemically unrelated inhibitors of lipolysis were used in order to differentiate between the effect of FFA depression and a possible FFA-unrelated drug effect, respectively, on the plasma concentrations of GH, cortisol, and glucagon. Saline infusion served as a control experiment. In eight healthy male volunteers, a similar FFA depression by either iv infusion of nicotinic acid (3-pyridine-carboxylic acid, NA) or oral intake of an adenosine derivative, N(6)-allyl-N(6)-cyclohexyl-adenosine (AD-D), was followed by a significant GH increase (to 22.1 +/- 6.2 and 9.6 +/- 2.9 ng/ml at 240 and 270 min, respectively). Due to the large scatter of the GH concentrations during NA infusion, these responses were not significantly different. No GH increase occurred when the FFA depression was prevented by addition of a lipid infusion. In contrast, plasma cortisol and glucagon both increased significantly (by 107.4 micrograms/liter at 270 min and by 48.4 pg/ml at 60 min, respectively) during NA- but not during AD-D-induced FFA depression. Addition of the lipid infusion abolished the cortisol increase during NA infusion but had no influence on basal cortisol concentrations during AD-D intake. It lowered glucagon to values slightly below basal concentrations when added to the NA infusion and more markedly during AD-D administration. The results provide evidence that 1) depression of plasma FFA per se stimulates the secretion of GH, and 2) the increase of cortisol and glucagon during NA infusion is probably unrelated to the FFA depression. Hence, the stimulatory effect of FFA lack on glucagon secretion needs to be reconsidered.
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PMID:Growth hormone, cortisol, and glucagon concentrations during plasma free fatty acid depression: different effects of nicotinic acid and an adenosine derivative (BM 11.189). 634 70

The influence of ketone body infusion on the serum GH and glucagon response to FFA depression and insulin hypoglycemia was investigated in 10 healthy men. Intravenous infusion of nicotinic acid induced suppression of both FFA and ketone bodies. This was accompanied by a delayed GH increase to 21.1 +/- 6.9 ng/ml (at 300 min). During an additional beta-hydroxybutyrate (OHB) infusion, FFA remained depressed, but ketone bodies were elevated, and the GH response was abolished (maximum 5.6 +/- 1.6 ng/ml). During infusion of OHB alone, FFA were suppressed. GH increased significantly, although less markedly than during suppression of both FFA and ketone bodies (to 9.3 +/- 3.1 ng/ml at 270 min). No GH rise occurred when both FFA and ketone bodies were kept elevated by the addition of a lipid infusion. The GH rise in response to insulin hypoglycemia was not changed by an OHB infusion (43.2 +/- 4.6 vs. 48.0 +/- 7.3 ng/ml). However, OHB increased the net GH output by significantly delaying the return to basal concentrations in the presence of a reduced FFA rebound. An effect of OHB infusion on the plasma glucagon concentration during all experiments was small, and its physiological significance is doubtful. These results confirm that FFA depression induces delayed GH secretion. They suggest that this is not wholly dependent on concomitant depression of ketone bodies. On the other hand, when ketone bodies are elevated, the GH response to FFA depression is diminished or absent. The net GH response to changes in lipid substrates probably depends on the concentration of both FFA and ketone bodies.
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PMID:Influence of ketone body infusion on plasma growth hormone and glucagon in man. 634 66

The antilipolytic activity of nicotinic acid was investigated in 7 patients with type II b hyperlipoproteinemia and in 7 with type IV hyperlipoproteinemia treated for two months with a nicotinic acid derivative, sorbinicate (1600 mg daily, ie 1454 mg NA). Before and after treatment the blood levels of total cholesterol and triglycerides were determined and three dynamic tests -- oral glucose tolerance test, insulin test and tolbutamide test -- were done to check in each test the variations in blood glucose, NEFA, insulin (excluding obviously the insulin test), glucagon and growth hormone levels. At the end of the treatment, there was a significant reduction of cholesterol (type IIb and type IV) and of triglycerides (type IV), a marked reduction of the glucagon response, a slight increase in the insulin response and in the basal secretion of the growth hormone. It is suggested that the antilipolytic activity of nicotinic acid (and hence of sorbinicate) is at least partly mediated by an inhibition of glucagon secretion (and/or synthesis).
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PMID:Possible glucagon-mediated hypocholesterolemic activity of a nicotinic acid derivative (sorbinicate). 666 Oct 43


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