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)

Glucagon was injected directly into the ventromedial hypothalamic nuclei (VMH) of rabbits, and changes in hepatic acetate metabolism were studied. The injection of 3 ng glucagon into the VMH of intact rabbits increased the rates of 14C transfer from 14C-1-acetate into CO2, glucose and ketone bodies but decreased those into cholesterol ester, triglyceride, free cholesterol, free fatty acids and phospholipids. However, after glucagon injection into the VMH of rabbits with VMH lesions and the parietal cortex of intact rabbits, hepatic acetate metabolism did not differ from that of the control rabbits, which received saline injection into the same brain regions. These observations support the hypothesis that the VMH are parts of a glucagon-sensitive brain regulator system in the hepatic acetate metabolism.
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PMID:Influence of microinjection of glucagon into ventromedial hypothalamus on acetate metabolism in liver slices of rabbit. 310 27

1. Whole-body, hind-limb and uterine tissue metabolism of glucose was studied using a combination of isotopic and arterio-venous difference techniques in shorn and unshorn pregnant sheep over the final 4 weeks of pregnancy. This was combined with the measurement of the concentrations of oxygen and carbon dioxide in arterial blood and plasma concentrations of lactate, acetate, non-esterified fatty acids, 3-hydroxybutyrate, glycerol, growth hormone (GH), insulin, glucagon, cortisol, thyroxine and 3,5,3'-triiodothyronine (T3). 2. Glucose entry rate was 28% higher in shorn ewes compared with unshorn controls, even though there was no difference in the arterial plasma concentration of glucose. This effect may have been caused by a decrease in the molar rate, insulin: glucagon (I:G), which was 40% lower in shorn ewes as a result of a significant decrease in the plasma concentration of insulin. There was no difference in the plasma concentration of cortisol or GH. 3. Blood flow across the hind-limb or uterine tissues was not significantly different between shorn and unshorn groups, neither were the net glucose uptake, glucose oxidation rate or contribution of glucose to O2 consumption across these tissues. 4. Insulin-tolerance tests performed on a separate group of shorn and unshorn ewes showed an increased sensitivity to the hypoglycaemic effects of insulin in the shorn group. 5. There was no significant difference between shorn and unshorn animals in the contribution of glucose to CO2 output or in the proportion of glucose entry rate oxidized. CO2 entry rate was 18% higher in shorn ewes compared with unshorn controls which resulted in a 26% higher estimated value for heat production. There was a 47% increase in glucose oxidation rate in shorn ewes but there was no significant difference in the proportion of total heat production which was derived from glucose. The arterial concentrations of O2 and CO2 were significantly higher in shorn ewes, which may be an indication of the higher metabolic rate in these animals. This effect may be mediated via a significant rise in plasma T3 concentration in the shorn group. 6. It is concluded that as a result of long-term cold exposure there is a significant increase in whole-body glucose entry and oxidation rates in the shorn pregnant ewe. The increase in insulin sensitivity at the same time as a decrease in plasma insulin concentration may represent a mechanism to ensure continued glucose supply to insulin-sensitive tissues while the concomitant decrease in plasma I:G stimulates hepatic gluconeogenesis.
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PMID:Glucose metabolism in shorn and unshorn pregnant sheep. 314 99

The determinants of the altered glucoregulation in acidosis were investigated in anesthetized dogs. Because CO2 rapidly equilibrates and its effects are mediated by pH changes, CO2 inhalation was examined. Plasma acid-base composition, glucose, insulin, glucagon, and blood flows were evaluated before and after an intravenous glucose load (1.2 +/- 0.1 g/kg body wt) in normal and acidotic dogs with flow probes and catheters chronically implanted in the portal circulation. A simultaneous infusion of phentolamine (5 micrograms.kg-1.min-1), propranolol (3.5 micrograms.kg-1.min-1), both, or none was used. All acidemic dogs had lower hepatic extraction of insulin and greater hyperglycemia after the glucose challenge; thus the adrenergic system is not critical for these responses. Because arterial insulin levels were either normal (propranolol) or increased (all others) in acidosis, insulin resistance was likely. Insulin infusion (2 and 4 mU.kg-1.min-1) with euglycemic clamp and [3-3H]glucose documented that acidemia decreases peripheral glucose utilization and the insulin suppression of hepatic glucose production. Acidemia also enhances plasma glucagon levels, yet this effect plays a limited role in the observed hyperglycemia.
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PMID:Acidosis-induced glucose intolerance is not prevented by adrenergic blockade. 314 81

The first branch point in gluconeogenesis occurs at the conversion of pyruvate to oxaloacetate. To determine the amount of lactate carbon reaching glucose via the direct pyruvate carboxylase pathway versus the tricarboxylic acid cycle, adult rat hepatocytes in primary culture were incubated for 2 h with one of the following isotopic substrates: [1-14C]lactate, [U-14C]lactate, or [1,2-14C]acetate. Production of 14CO2 and [14C]glucose from each substrate was assessed. The amount of lactate carbon 2 and 3 incorporated into glucose or oxidized to CO2 was determined by subtracting values using [1-14C]lactate from those using [U-14C]lactate. After quantitation of CO2 formed from carbons 2 and 3 of lactate, the amount of these carbons incorporated into glucose via the tricarboxylic acid cycle can be determined by simple proportionality from the ratio of label incorporated into glucose or CO2 from [1,2-14C]acetate. The remaining carbons 2 and 3 of lactate incorporated into glucose are derived from the pyruvate carboxylase pathway directly. Ethanol which on oxidation provides NADH and acetate decreased lactate oxidation and enhanced the pyruvate carboxylase pathway. Glucagon increased carbon flux through both pathways but primarily through the pyruvate carboxylase pathway. In summary, a simple model is presented to examine carbon flux from lactate via the pyruvate carboxylase and tricarboxylic acid pathways during gluconeogenesis.
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PMID:Model to examine pathways of carbon flux from lactate to glucose at the first branch point in gluconeogenesis. 318 10

The intrinsic processes involved in the initiation and arrest of seizures are not completely understood. Cortical and cerebellar inhibitory mechanisms, accumulation of metabolic products, and glial uptake of extracellular potassium (K+o), anions, and released neurotransmitters are all important processes that limit focal firing and terminate a seizure once it has been initiated. Of these, the intrinsic cortical inhibitory mechanisms--i.e., recurrent and surround inhibition--appear to be the most important. Active cation and anion transport processes are two metabolic events that have yet to be elucidated but clearly could be involved in terminating a seizure discharge. For example, without an active mechanism to transport chloride, opening of the chloride channel by the inhibitory transmitter GABA would not result in increased chloride permeability. The transient hypoxia and hypercapnia and lactic acidosis that follows a severe tonic-clonic seizure produces a mixed systemic metabolic and respiratory acidosis. In experimental animals, the hypercapnia that results is sufficient to block seizure discharges. Increasing the CO2 concentration significantly reduces the extension to flexion (E/F) ratio of mice given maximal electroshock seizures (MES) and increases the time required for 50% of the animals to recover sufficiently from a first MES to be able to have another MES. The decreased E/F ratio and the increased recovery time (RT50) are both indicative of a decrease in seizure activity. Since the extent to which CO2 is allowed to accumulate in the brain is regulated by the glial specific enzyme carbonic anhydrase (CA), it follows that the glial cell has an integral role in the mechanisms involved in arresting seizure activity. In contrast, hypoxia increased the E/F ratio and decreased the RT50, evidence that seizure activity was enhanced. Another metabolic factor affecting duration of seizure activity, susceptibility to seizures, and recovery from seizures is glucose. Recovery from seizures depends in part on an adequate supply of this energy source. An inverse correlation (R = 0.95) between RT50 and blood sugar was found when the blood sugar was altered experimentally by treatments that altered the endocrine status (pancreatectomy, treatment with alloxan, cortisol, insulin, glucagon, and dextrose). Since glial cells contain (as glycogen) the small amount of glucose present in the brain, they probably hasten the ability of the brain to recover normal function following a seizure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of glial cation and anion transport mechanisms in etiology and arrest of seizures. 370 23

The ventilatory responses to catecholamine infusions have been well studied. Increases in plasma levels of cortisol and glucagon during stress may exert a synergistic effect with epinephrine. We examined the effect of epinephrine and a combined hormone infusion in four normal postabsorptive subjects. On three separate occasions each subject was assigned randomly to receive a 5.5-h infusion of saline (control), epinephrine (1.2 micrograms/m2 . min), or epinephrine plus cortisol (5 mg/m2 . min) plus glucagon (3 mg/kg . min). Oxygen consumption (VO2), CO2 production, minute ventilation (VE), tidal volume (VT), frequency (f), inspiratory flow, and inspiratory time during room-air breathing and inhalation of 2% and 4% CO2 were measured before infusion and during the last 2 h of infusion, using a noninvasive canopy system. VO2 increased significantly (p less than .05) from the control condition during both combined and epinephrine infusions (23% and 11%, respectively). The increase in VE was related linearly to the increase in VO2, and was primarily due to an increase in VT; however, there was a small rise in f. The VE-PaCO2 regression during CO2 inhalation was shifted leftward to an equal degree during both infusions. These data indicate that cortisol and glucagon augment the calorigenic action of epinephrine; ventilatory effects are augmented in relation to the changes in VO2.
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PMID:Ventilatory effects of the stress hormones in normal man. 372 Mar 7

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2-3H]glycerol and [1-14C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1-13C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.
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PMID:Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion. 389 May 59

Hepatocytes were isolated from the livers of fed rats and incubated, in the presence and absence of 100 nM-glucagon, with a substrate mixture containing glucose (10 mM), fructose (4 mM), alanine (3.5 mM), acetate (1.25 mM), and ribose (1 mM). In any given incubation one substrate was labelled with 14C. Incorporation of 14C into glucose, glycogen, CO2, lactate, alanine, glutamate, lipid glycerol and fatty acids was measured after 20 and 40 min of incubation under quasi-steady-state conditions [Borowitz, Stein & Blum (1977) J. Biol. Chem. 252, 1589-1605]. These data and the measured O2 consumption were analysed with the aid of a structural metabolic model incorporating all reactions of the glycolytic, gluconeogenic, and pentose phosphate pathways, and associated mitochondrial and cytosolic reactions. A considerable excess of experimental measurements over independent flux parameters and a number of independent measurements of changes in metabolite concentrations allowed for a stringent test of the model. A satisfactory fit to the data was obtained for each condition. Significant findings included: control cells were glycogenic and glucagon-treated cells glycogenolytic during the second interval; an ordered (last in, first out) model of glycogen degradation [Devos & Hers (1979) Eur. J. Biochem. 99, 161-167] was required in order to fit the experimental data; the pentose shunt contributed approx. 15% of the carbon for gluconeogenesis in both control and glucagon-treated cells; net flux through the lower Embden-Meyerhof pathway was in the glycolytic direction except during the 20-40 min interval in glucagon-treated cells; the increased gluconeogenesis in response to glucagon was correlated with a decreased pyruvate kinase flux and lactate output; fluxes through pyruvate kinase, pyruvate carboxylase, and phosphoenolpyruvate carboxykinase were not coordinately controlled; Krebs cycle activity did not change with glucagon treatment; flux through the malic enzyme was towards pyruvate formation except for control cells during interval II; and 'futile' cycling at each of the five substrate cycles examined (including a previously undescribed cycle at acetate/acetyl-CoA) consumed about 26% of cellular ATP production in control hepatocytes and 21% in glucagon-treated cells.
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PMID:Quantitative analysis of intermediary metabolism in hepatocytes incubated in the presence and absence of glucagon with a substrate mixture containing glucose, ribose, fructose, alanine and acetate. 391 12

We have investigated the effect of infusion of DL-beta-hydroxybutyrate (BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA) metabolism by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In one group hormones were not controlled, while in the other two groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin, and glucagon at constant rates. In one of these hormonally controlled groups, combined alpha- and beta-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration approximately 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. However, when sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. We conclude from these studies that an elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.
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PMID:Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs. 609 72

We have developed a method to circumvent the use of exogenous proteolytic enzymes in the isolation of islets of Langerhans from the perinatal rodent pancreas. Advantage is taken of the propensity of fibroblastlike cells to attach and migrate on polystyrene at low-serum concentrations (5%). In contrast, at this serum level, rat islet epithelial cells tend not to adhere to the substrate. At 3 d of culture, islets are visible at the edges of the explants. With further fibroblast outgrowth the majority of islets are freefloating by 7 d. Simple agitation of the medium and centrifugation yields approximately 50 micrograms of islet tissue per perinatal pancreas. Further purification of the islets can be obtained by subculture. Rat islets can be maintained in this manner for several months in Medium F12 supplemented with 25% horse serum in an atmosphere of 5% CO2 and air at 37 degrees C. Hormone content of the islet tissue remains constant during prolonged subculture and such islets continue to exhibit appropriate insulin and glucagon responses to glucose and theophylline. The morphological integrity of the endocrine cells within the cultured islets was confirmed by immunocytochemistry and ultrastructural study. Nonendocrine cells are not identifiable within the long-term cultured islets.
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PMID:Nonenzymic in vitro isolation of perinatal islets of Langerhans. 613 59


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