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 effects of exogenous (IV Norepinephrine (NE)) and endogenous alpha adrenergic activity (IV phentolamine (PH)) were studied in the duck. Our aim was first to compare their importance in animals fed for 1 1/2 hours and fasted for 24 and 48 hours, and then to assess the relative importance of alpha versus beta adrenergic receptor mediated effects during the development of a 48-hour-fast. NE reduces plasma IRI levels after a fast but not in the postprandial state. PH while ineffective in animals fed for 1 1/2 hours brings fasting IRI values to levels observed in the former group. Twenty-four hour fasted ducks are sensitive to both alpha adrenergic stimulation and beta adrenergic blockade which have additive effects; so, insulin secretion is controlled by 2 distinct mechanisms: a beta stimulating and an alpha inhibiting one. The importance of one component versus the other is modulated by the nutritional state: indeed, a double alpha and beta equimolar adrenergic blockade reveals that during the transition from the postprandial state to a 48-hour-fast, there is a progressive reversal in the importance of one adrenergic component versus the other. The effects of alpha adrenergic stimulation or blockade occur independently of simultaneous glucose variations. This is not the case for A cell function: an alpha adrenergic receptor stimulating effect on glucagon secretion exists, but A cell remains primarily sensitive to plasma glucose level. alpha Adrenergic activity has no direct effect on plasma free fatty acids (FFA) level but plays a role in plasma glucose level regulation especially in animals in the postprandial state.
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PMID:Modulation by the nutritional state of adrenergic receptor mediated effects on insulin secretion in ducks. 675 51

The effects of glucagon and norepinephrine on gluconeogenesis by perfused chicken liver were studied with fluorimetric monitoring of the redox states of the intracellular pyridine nucleotides. Glucagon stimulated glucose production from precursors entering the pathway both above and below the level of triose phosphates without causing a detectable effect on the redox states of pyridine nucleotides. Glucagon stimulation was not abolished by subsequent infusion of octanoate or ethanol. The presence of a pyruvate/lactate mixture plus NH4Cl resulted in a maximum efficacy of glucagon. Glucose production from lactate and fructose was stimulated by norepinephrine. Norepinephrine always caused a change towards increased reduction of pyridine nucleotides with an increase in the beta-hydroxybutyrate/acetoacetate ratio, but displayed no stimulation of glucose and lactate production from pyruvate. As a result of octanoate infusion with lactate, the changes induced by norepinephrine were reversed. The responses to norepinephrine and phenylephrine were decreased markedly in liver perfused with a calcium-free medium and/or with phentolamine. Infusion of calcium into the calcium-deficient liver caused an abrupt elevation of glucose production together with a reduction of pyridine nucleotides, and the original response to norepinephrine was recovered. The results demonstrate that the effects of glucagon and norepinephrine on gluconeogenesis are not identical, and that norepinephrine stimulation is mediated through an alpha-adrenergic and calcium-dependent mechanism in which redox changes of mitochondrial pyridine nucleotides are involved.
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PMID:Stimulation of gluconeogenesis by glucagon and norepinephrine in the perfused chicken liver. 711 65

The role of the cellular redox state in the hormonal stimulation of gluconeogenesis was studied in hemoglobin-free perfused rat liver, by fluorimetric measurement of the redox states of intracellular pyridine nucleotides. The maximum rate of glucose production from lactate/pyruvate mixture was observed with a lactate/pyruvate ratio of 10/1, which corresponds to the ratio observed in vivo. Increased reduction of pyridine nucleotides on infusion of ethanol or octanoate was associated with an increased production of glucose from pyruvate, whereas glucose production from lactate decreased. Stimulation of gluconeogenesis from lactate by glucagon was affected by the lactate/pyruvate ratio; a decrease of the lactate/pyruvate ratio resulted in a decrease of the efficacy of glucagon. Stimulation by glucagon of glucose production from pyruvate was abolished during octanoate infusion, although it was still observable during ethanol infusion. In contrast to glucagon, the stimulatory effect of norepinephrine on gluconeogenesis was unaffected by the ratio of lactate to pyruvate. Norepinephrine in the presence of octanoate and ethanol still induced stimulation of glucose production from lactate and pyruvate, which was always accompanied by a transient reduction of pyridine nucleotides. The results demonstrate that the regeneration of NADH in the cytosol is one of the regulatory factors in gluconeogenesis, and that the effects of glucagon and norepinephrine on gluconeogenesis and on the redox state of pyridine nucleotides are not identical.
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PMID:Intracellular redox state and stimulation of gluconeogenesis by glucagon and norepinephrine in the perfused rat liver. 735 25

The isolated, perfused, canine stomach was used to investigate the effect of three neurotransmitters--norepinephrine, acetylcholine (or its analogue carbamylcholine), and VIP (vasoactive intestinal peptide)--on gastric glucagon release. Norepinephrine at the two concentrations tested (3.10-8 and 7.10-7 M) did not influence gastric glucagon release. In contrast, acetylcholine or carbamylcholine (5.10-6 M) as well as VIP (46-60 ng/ml) unequivocally stimulated gastric glucagon release, an effect apparently independent of the changes in blood flow. These results are in sharp contrast with the previously reported lack of effect of an electric stimulation of the vagus nerves on the release of glucagon from the dog stomach. An absence of innervation of the canine gastric A-cell would probably best explain this situation.
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PMID:Neurotransmitters and glucagon release from the isolated, perfused canine stomach. 743 45

In fetal sheep, prolonged hypoxia (for 24 h) induced by a reduction in maternal uterine artery blood flow, increases insulin-like growth factor binding protein-1 (IGFBP-1) levels and decreases IGFBP-2 levels in the plasma, with corresponding changes in messenger RNA (mRNA) levels in the liver. Since IGFBP-1 synthesis in liver cells in vitro is stimulated by compounds that increase intracellular cAMP concentrations, we hypothesized that the increased IGFBP-1 synthesis during prolonged hypoxemia may be induced by circulating catecholamines, that are released during hypoxia, and that elevate fetal liver cAMP levels. Our aim was to determine the effect of 24-h catecholamine infusions on the synthesis and release of IGFBP-1 and IGFBP-2 in fetal sheep. Vascular catheters were implanted into fetuses at 110-115 days gestation in 14 pregnant ewes. After a 5-day recovery period, fetuses received a 24-h infusion of either norepinephrine (1 micrograms/kg.min, n = 5), epinephrine (0.25 micrograms/kg.min, n = 5), or vehicle (normal saline, n = 4). Fetal carotid arterial samples were collected at specified intervals throughout the infusion for the determination of blood glucose concentrations, plasma catecholamine concentrations by HPLC, insulin, and glucagon concentrations by RIA, and IGFBP levels by Western ligand blotting. After 24 h, the ewe and fetus were killed and selected fetal tissues (liver and kidney) were collected, and analyzed for IGFBP mRNA levels by northern blotting followed by laser densitometric quantification. Plasma catecholamine concentrations were increased in treated fetuses to levels that may be expected in fetuses subjected to prolonged hypoxia. In epinephrine and norepinephrine infused fetuses, blood glucose and plasma glucagon concentrations were increased significantly, whereas plasma insulin concentrations were decreased significantly. Norepinephrine and epinephrine infusions increased IGFBP-1 levels significantly (2- to 5-fold) in fetal plasma within 8-12 h, and the time course pattern of elevation of plasma IGFBP-1 levels was similar to that observed in prolonged hypoxia. After 24 h of either norepinephrine or epinephrine infusion, IGFBP-1 mRNA levels in the liver of fetuses were increased significantly (5- to 7-fold) compared to those of vehicle infused fetuses. IGFBP-2, -3, and -4 levels in fetal plasma were not affected by either infusion, nor were IGFBP-2 mRNA levels in fetal liver and kidney.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Catecholamines stimulate the synthesis and release of insulin-like growth factor binding protein-1 (IGFBP-1) by fetal sheep liver in vivo. 750 34

Two modes of heat production exist which are involved in body temperature regulation with decreasing environmental temperature: shivering thermogenesis and more efficient nonshivering thermogenesis (NST). Enhanced NST is mediated by the activated sympathetic nervous activity and increased secretions of hormonal factors such as glucagon through an enhanced lipid utilization. Moreover, cold acclimation causes an increased responsiveness of the organism to these factors. Noradrenaline-induced secretion of glucagon is also enhanced by cold acclimation. Chronic administration of glucagon simulates cold acclimation, resulting in an improved cold tolerance by an increased NST. Brown adipose tissue (BAT) is a major site for nonshivering thermogenesis (NST) during metabolic cold acclimation. Cold acclimation causes a hyperplasia as well as an enhanced metabolic capacity of BAT cell. BAT function is mainly regulated by sympathetic noradrenaline and several hormonal factors such as glucagon. BAT possesses rich blood supply by which its high thermogenic capacity and an efficient transfer of heat are maintained. Noradrenaline and glucagon increases not only heat production, but also blood flow in BAT. Nitric oxide (NO), endothelium-derived relaxing factor, is involved in noradrenaline-, glucagon- and cold-induced increases of blood flow through BAT. Noradrenaline-induced BAT thermogenesis is suggested to be mediated by NO. NO synthase occurs in BAT cell in addition to endothelium of BAT vessel. These findings indicate that NO may be a signalling molecule for an enhanced NST during cold acclimation. Moreover, BAT contributes to adaptation to overfeeding, nonthermal stress and fever by means of producing heat, playing a role as adaptive organ in overall energy metabolism.
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PMID:[Regulation of thermoregulatory thermogenesis]. 774 60

The effect of sucrose overfeeding and low iron diet on brown adipose tissue (BAT) thermogenesis of rats has been investigated from the view point of in vitro BAT oxygen consumption and BAT fatty acids (FA) compositions in rats. Control group was fed on a standard diet with tap water, sucrose group was on the standard diet and 32% sucrose solution, and iron deficient group on a low iron diet with tap water. In vitro interscapular BAT thermogenesis as estimated by oxygen consumption was measured in minced tissue blocks in Krebs-Ringer phosphate buffer using a Clark oxygen electrode. In sucrose overfeeding rats, caloric intake was greater than in controls, but did not differ body weight. Interscapular BAT weight and DNA content were greater. Colonic and tail skin temperatures were higher. Basal oxygen consumption was higher. Noradrenaline- and glucagon-stimulated oxygen consumptions did not differ when expressed per DNA, but significantly greater per whole tissue pad. Both BAT-triglyceride (TG) and -phospholipid (PL) levels were higher. Polyunsaturated FA were lower, while monosaturated FA were higher in both BAT-TG and -PL. In iron deficient rats, BAT weight and DNA content were higher. Colonic and tail skin temperatures did not differ. Although basal oxygen consumption did not differ, noradrenaline-stimulated oxygen consumption was less per DNA, but did not differ per whole tissue pad, while glucagon-stimulated oxygen consumption was less when expressed per DNA, as well as whole tissue pad. Cold-tolerance as assessed by the fall in colonic temperature at 0 degree C was decreased. BAT-TG and -PL levels did not differ. Polyunsaturated FA were higher in both BAT-TG and -PL. These findings indicated that sucrose-induced overfeeding enhances BAT thermogenesis mainly by tissue hyperplasia, while iron deficiency suppresses BAT thermogenic response, although it causes the compensatory tissue hyperplasia.
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PMID:[Nutritional adaptation in brown adipose tissue thermogenesis--with special reference to overfeeding and iron deficiency]. 786 52

To determine if exercise intolerance and fatigue in chronic heart failure could be exacerbated by an abnormal metabolic response to exercise, we studied 12 patients with stable chronic heart failure and 12 normal volunteers during symptom-limited maximal treadmill exercise. Peak VO2 was 17.2 (15.1-19.2) ml.kg-1 x min-1 in patients and 29.9 (26.3-33.5) in controls (mean and 95% confidence intervals; P < 0.0001, t-test). Overall, levels in peripheral venous blood of glucose, glycerol and free fatty acids were greater in patients, although the differences became less marked with increasing exercise intensity. Noradrenaline was elevated in patients at rest, but the peak exercise response was similar to controls. Responses of adrenaline, insulin and glucagon were similar in both groups. We conclude that depletion of the levels of circulating substrates is not contributory to exercise intolerance and fatigue in chronic heart failure. Greater levels of glycerol and free fatty acids may be mediated by excess sympathetic nervous system activity, reflected in elevated noradrenaline levels.
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PMID:Metabolic responses to graded exercise in chronic heart failure. 829 29

The effects of catecholamines (CATS) infused into the hepatic portal vein were studied in ten 18-h-fasted conscious dogs. Glucose production (GP) and gluconeogenesis (GNG) were assessed using tracer ([3H]glucose, [14C]alanine) and arteriovenous difference techniques. Each experiment consisted of a 100-min equilibration, a 40-min basal, and two 90-min test periods. A pancreatic clamp (somatostatin + basal portal insulin and glucagon) was used to fix insulin and glucagon at basal levels. Propranolol (1 microgram.kg-1.min-1) and phentolamine (2 micrograms.kg-1.min-1) were infused intraportally during both test periods of the blockade group while a carrier solution was infused in the control group. Norepinephrine (NE; 100 ng.kg-1.min-1) and epinephrine (Epi; 40 ng.kg-1.min-1) were infused intraportally during the second test period of both protocols. Portal NE (70 +/- 46 to 8,404 +/- 674 and 162 +/- 57 to 6,530 +/- 624 pg/ml, respectively) and portal Epi (21 +/- 11 to 3,587 +/- 309 and 29 +/- 6 to 2,989 +/- 406 pg/ml, respectively) rose in the control and adrenergic blockade groups, respectively. The increases in arterial NE and Epi were modest in both groups. Intraportal infusion of CATS increased GP from 2.1 +/- 0.2 to 6.2 +/- 1.0 mg.kg-1.min-1 in the control group but did not change it (2.7 +/- 0.4 to 2.7 +/- 0.3 mg.kg-1.min-1) in the blockade group. Portal CATS had no effect on GNG in the presence or absence of adrenergic blockade (GNG rose from 0.7 +/- 0.2 to 0.9 +/- 0.2 and 0.8 +/- 0.2 to 1.0 +/- 0.2 mg.kg-1.min-1 in the control and blockade groups, respectively). In conclusion, portal infusion of catecholamines significantly augmented GP by selectively stimulating glycogenolysis. The increase in hepatic GP could be completely inhibited by intraportal adrenergic blockade.
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PMID:Direct effects of catecholamines on hepatic glucose production in conscious dog are due to glycogenolysis. 876 90

We have previously demonstrated that the liver can release glucose in response to insulin-induced hypoglycemia, despite the absence of glucagon, epinephrine, cortisol, and growth hormone. The aim of this study was to determine whether this is activated by liver or brain hypoglycemia. We assessed the response to insulin-induced hypoglycemia in the absence of counterregulatory hormones in overnight-fasted conscious adrenalectomized dogs that were given somatostatin and intraportal insulin (30 pmol x kg(-1) x min(-1)) for 360 min. Glucose was infused to maintain euglycemia for 3 h and then to allow limited peripheral hypoglycemia for the next 3 h. During peripheral hypoglycemia, five dogs received glucose via both carotid and vertebral arteries to maintain cerebral euglycemia (H-EU group) concurrently with peripheral hypoglycemia, while six dogs received saline in these vessels to allow simultaneous cerebral and peripheral hypoglycemia (H-HY group). Throughout the study, arterial insulin was 1,675 +/- 295 and 1,440 +/- 310 pmol/l in the H-HY and H-EU groups, respectively. Glucose fell from 6.2 +/- 0.3 to 2.1 +/- 0.0 mmol/l and from 5.8 +/- 0.3 to 1.9 +/- 0.1 mmol/l in the last hour in the H-HY and H-EU groups, respectively (P < 0.05 for both). Norepinephrine rose from 1.12 +/- 0.35 to 2.44 +/- 0.69 nmol/l and from 1.09 +/- 0.07 to 1.74 +/- 0.16 nmol/l in the last hour in the H-HY and H-EU groups, respectively (P < 0.05 for both; no difference between groups). Glucagon, epinephrine, and cortisol were below the limits of detection. The liver switched from uptake to output of glucose during peripheral hypoglycemia in both the H-HY (-7.1 +/- 2.1 to 5.4 +/- 3.1 micromol x kg(-1) x min(-1)) and H-EU (-7.9 +/- 3.5 to 3.4 +/- 1.7 micromol x kg(-1) x min(-1)) groups (P < 0.05 for both; no difference between groups). Alanine levels and net hepatic alanine uptake fell similarly in both groups. There were increases (P < 0.05) in glycerol (12 +/- 3 to 258 +/- 47 micromol/l) and nonesterified fatty acid (194 +/- 10 to 540 +/- 80 micromol/l) levels and in total ketone production (0.4 +/- 0.1 to 1.1 +/- 0.2 micromol x kg(-1) x min(-1)) in the H-HY group, but these parameters did not change in the H-EU group. These data clearly indicate that the lipolytic and hepatic responses to hypoglycemia are driven by differential sensing mechanisms. Thus, during insulin-induced hypoglycemia, when counterregulatory hormones are absent, liver hypoglycemia triggers the increase in hepatic glucose production, whereas cerebral hypoglycemia causes the increases in lipolysis and ketogenesis.
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PMID:In the absence of counterregulatory hormones, the increase in hepatic glucose production during insulin-induced hypoglycemia in the dog is initiated in the liver rather than the brain. 892 69


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