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)

Rats were acutely administered ethanol as a primed constant infusion in order to produce sustained blood ethanol levels of 8-12 or 55-65 mM. At the end of ethanol infusion the livers were either freeze-clamped in vivo or isolated and perfused for metabolic studies. The rate of gluconeogenesis and its responsiveness to phenylephrine (10 microM), prostaglandin F2 alpha (5 microM) and glucagon (10 nM), as well as the redox state of the cytosolic NAD(+)-NADH system were assessed in livers isolated from acutely ethanol-treated rats, and subsequently perfused without ethanol. For liver clamped in vivo, high- but not low-ethanol treatment decreased the ATP content by 31% and slightly increased ADP and AMP content, resulting in a decreased energy charge (11%). Glutamate and aspartate content was also increased in high-dose ethanol-infused rats with no changes in malate and 2-oxoglutarate content. Gluconeogenesis with saturating concentrations of lactate (4 mM)+pyruvate (0.4 mM) was delayed in reaching a plateau in the livers of high-dose ethanol-treated rats and its response to all three stimulators was impaired. Low-dose ethanol treatment only decreased the liver response to phenylephrine. While the perfused livers of low-dose ethanol-treated rats displayed no changes in adenine nucleotide content, the livers of high-dose ethanol-treated rats had a decreased ATP (35%) and an increased AMP (77%) content, paralleled by a fall in the total adenine nucleotides (14%) and energy charge (14%). No differences were observed between the saline- and ethanol-treated rats with respect to malate-aspartate shuttle intermediate concentration in perfused livers. Also, the livers of high-, but not low-dose ethanol-treated rats had a more negative value of NAD(+)-NADH redox state as compared to the livers of control rats. The data suggest that acute ethanol intoxication produces changes in liver metabolism and its responsiveness to hormones/agonists that are demonstrable for at least 2 hr after isolation and perfusion of the liver.
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PMID:Effects of acute alcohol intoxication on gluconeogenesis and its hormonal responsiveness in isolated, perfused rat liver. 135 76

Experimental therapies for McArdle's disease have been directed toward increasing substrate availability to exercising muscle. Such therapies to date have proven largely unsuccessful. These include administration of isoproterenol to increase blood flow, glucagon treatment to elevate serum glucose and increased dietary fat intake. Each of these therapies also results in greater levels of unesterified fatty acids in blood. More recently, a high protein diet is suggested to provide increased amounts of amino acids which would be available as fuel sources. We hypothesize that the absence of myophosphorylase in McArdle's disease creates an imbalance between the enzymes of the redox systems that control the generation, propagation and inactivation of free radicals. This occurs because muscle cells are forced to rely more heavily on fatty acid oxidation. The resulting free radical damage to cellular components disrupts metabolic control and increases the permeability of membranes. Elevated levels of Ca2+ in the sarcoplasm activate proteases, phospholipases and other catabolic enzymes initiating muscle fatigue and cramping. Lipid peroxidation is a consequence of normal muscle activity and may occur unchecked in individuals with McArdle's disease. Continued muscle activity in the absence of a favorable nutritional environment may promote the progression of the disease by increasing susceptibility to oxidative stress.
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PMID:The role of lipid peroxidation in McArdle's disease: applications for treatment of other myopathies. 146 Nov 77

A 31-year-old male patient with type Ia glycogen storage disease was admitted to our department complaining of general fatigue and right hypochondriac pain. He exhibited massive hepatomegaly with systemic hypoglycemia, lactic acidosis, hyperuricemia, hyperpyruvatemia and hyperlipemia. The failure of blood glucose levels to increase after a glucagon loading test, and a reduced lactate level on glucose tolerance test were also observed. Various imaging techniques suggested hepatic adenoma with hemorrhage in the tumor, which was confirmed histologically. There was a complete absence of glucose 6-phosphatase activity, as determined by an enzyme assay on resected liver specimens, which proved the case to be type Ia glycogen storage disease. We also reviewed all previously reported cases of hepatic tumor and glycogen storage diseases. We conclude that, since hepatic adenoma is not rare in this disease, and is complicated by hemorrhage, rupture and malignancy, careful follow-ups are necessary.
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PMID:A case of type Ia glycogen storage disease complicated by hepatic adenoma. 217 Feb 59

Six patients (four females, two males; aged 18-65 years), previously treated by external pituitary irradiation (2000-4000 cGY in 8-15 fractions over 10-20 days) for pituitary tumours, presented with the symptoms of excessive and inappropriate tiredness suggestive of ACTH deficiency, despite a normal peak cortisol response to an insulin tolerance test (four cases) or to a glucagon stimulation test (two cases). These six patients were found to have significantly lower mean 24 h urinary free cortisol levels (100 +/- 40 nmol; mean +/- SD) compared with the mean value of 31 normal controls (210 +/- 70.8 nmol; P less than 0.01). In addition serum cortisol profiles based on a series of four timed samples between 0900-2300 h were subnormal (mean 130 nmol/l) in comparison with profiles obtained from 12 normal controls (mean 270 nmol/l) (P less than 0.001). Glucocorticoid replacement therapy promptly abolished their symptoms. These results suggest that a discordance between ACTH secretion under basal circumstances and ACTH response to pharmacological tests may exist in patients with ACTH deficiency. We speculate that defective endogenous corticotrophin-releasing hormone (CRF) secretion, due to radiation-induced damage at hypothalamic level, is one cause of this phenomenon.
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PMID:Adrenocorticotrophin (ACTH) deficiency undetected by standard dynamic tests of the hypothalamic-pituitary-adrenal axis. 284 48

Hypoglycaemia (blood glucose 1.3-2.5 mmol/l) was induced in twenty-eight diabetic children by reduction of their morning meal. Fatigue and pallor were the most common signs of hypoglycaemia. Compared to findings during normoglycaemia, plasma concentrations of adrenalin, noradrenalin and cortisol were significantly higher at glucose nadir. Plasma glucagon concentration at glucose nadir was correlated to the fasting C-peptide concentration and inversely to the duration of diabetes. Children who lacked C-peptide also lacked glucagon response to hypoglycaemia. The parents' opinion of the need to give carbohydrates corresponded to the blood glucose level. The presence of adrenergic signs correlated to the plasma adrenalin and the neuroglucopenic signs to blood glucose. The lowest glucose level correlated inversely to the concentration of free insulin. When facilities for glucose infusion are lacking, a rational step in treating the unconscious hypoglycaemic child seems to be the injection of glucagon, considering the blunted or absent glucagon secretion.
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PMID:Hypoglycaemia in childhood diabetes. I. Clinical signs and hormonal counterregulation. 329 49

Six Holstein cows were sampled hourly for 24 h for plasma concentrations of hormones and metabolites. Cows were sampled at about 2 wk prepartum, at 3 wk postpartum, during a ketonemia induced by feed restriction to 54% of ad libitum intake, and after a recovery period. They were fed long alfalfa hay postpartum. The onset of lactation caused concentrations of growth hormone, glucagon, acetoacetate, beta-hydroxybutyrate, and total amino acids of plasma to increase and those of glucose and insulin to decrease. Feed restriction exacerbated changes at 3 wk postpartum except for total amino acids and glucagon, which both decreased to prepartal concentrations. Resumption of ad libitum feeding caused most hormones and metabolites to return to prepartum concentrations. Diurnal variations in response to feeding twice daily were most evident for growth hormone, free fatty acids, and total amino acids. The 3-wk postpartum and ketonemic periods gave the greatest responses to feeding. Molar ratios of insulin to glucagon and insulin to growth hormone tended to decrease at 3 wk postpartum and decreased further in ketonemia, demonstrating hormonal adaptations to decreased energy intake during lactation. Lactation ketosis results from more than severe energy deficit.
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PMID:Glucagon, insulin, growth hormone, and some blood metabolites during energy restriction ketonemia of lactating cows. 388 31

To determine the possible role of altered secretion and effects of insulin in fuel homeostasis during heat exposure, the hormonal and metabolic milieu of three groups of rats were studied. The first was placed at 35 degrees C for 12 days (HE), the second was pair-fed (PF) to the first but maintained at 23 degrees C, and the third was allowed to eat ad libitum at 23 degrees C (C). Plasma insulin, glucagon, glucose, and free fatty acids (FFA), and blood lactate, pyruvate, 3-hydroxybutyrate, and individual amino acids were determined. To further characterize glucoregulation, an intraperitoneal glucose tolerance test (1 mg/g body wt) and isotopic glucose turnover (primed infusion of [3-3H]glucose) were performed. In HE rats, weight was constant for the last third of the period, and metabolic state 4 h after food removal was characterized by euglycemia but hypoinsulinemia, elevated blood pyruvate and FFA, and normal 3-hydroxybutyrate compared with C. Lowered levels of branched-chain amino acids and arginine were found. Fourteen hours after food removal glucose turnover was decreased. However, glucose intolerance accompanied by hyperinsulinemia was also found. Many of these changes were also seen in PF, including constant weight, fasting euglycemia, hypoinsulinemia, elevated FFA, and lowered valine and isoleucine. In contrast, pyruvate concentrations were normal, that of 3-hydroxybutyrate was elevated, and the decrement in glucose turnover was smaller than in HE rats. The glucose tolerance was similar to that of HE but accompanied by hypoinsulinemia. The results in HE suggest decreased energy metabolism, insulin secretion altered in a complex manner, and altered insulin action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucoregulatory and metabolic responses to heat exposure in rats. 637 8

Beta-blockade is known to induce muscle fatigue and tendency to hypoglycaemia during prolonged exercise. In addition, beta-blocking agents influence the secretion of many hormones, which regulate glucose. We have investigated the effects of a beta 1-selective (metoprolol) and a non-selective (propranolol) beta-blocking agent on muscle glycogenolysis, blood glucose and lactate levels, plasma levels of free fatty acids and on secretion of insulin, growth hormone, glucagon and cortisol during physical exercise in a double blind cross-over study in seven healthy male volunteers. They participated in three bicycle ergometer tests each lasting for 30 minutes under treatment of placebo (C), metoprolol (M) or propranolol (P). A biopsy was obtained from the vastus lateralis muscle before and immediately after the exercise for muscle glycogen assay. The glycogen concentration after exercise tended to be lower in C than in M or P experiment. The blood glucose level decreased during P and at 30 min there was a significant difference between P and C. The blood lactate was significantly lower before exercise during P than C or M. The increase of blood lactate during exercise, however, was not inhibited by P. Both beta-blocking agents counteracted the increase of FFA during exercise. There was a marked increase of growth hormone secretion during beta-blockade. The secretion of glucagon and cortisol were slightly increased by P and M, but the plasma insulin level was not affected by beta-blockade.
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PMID:Modification of the metabolic and hormonal response to physical exercise by beta-blocking agents. 675 73

Our objective was to assess the effects of increased propionate supply on gut and liver function in lactating cows. Four multicatheterized, primiparous cows (30.4 +/- .5 kg/d of milk) were fed for ad libitum intake a diet of 50% alfalfa hay and 50% concentrate (20.6 +/- 1.9 kg/d of DM, 226 +/- 21 MJ/d of metabolizable energy, and 611 +/- 56 g/d of N). Each cow received intramesenteric infusions of NaCl (control) or Na-propionate (150 mmol/h of a 2.5 M solution) in a reversal design. After 72 h of infusion, blood flow (by indicator dilution) and net flux (venoarterial differences multiplied by blood flow) were measured across portal-drained viscera and the liver. Energy supply from feed consumed and from infusion was similar between treatments. Energy that was excreted as milk decreased with propionate infusion. Propionate infusion increased arterial concentration of propionate; decreased absorption of acetate, butyrate, and valerate; and decreased hepatic removal of L-lactate, butyrate, valerate, NEFA, and oxygen. Propionate infusion decreased splanchnic release of glucose and increased splanchnic release of acetate and alanine. Net flux of urea, BHBA, insulin, or glucagon was unaffected by treatments. Our data show a link between a greater proportion of energy supplied as propionate and decreased energy excreted as milk. This response was associated with decreased net removal of glucogenic and ketogenic substrates by the liver and increased supply of acetate for use by peripheral tissues.
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PMID:Effect of mesenteric vein infusion of propionate on splanchnic metabolism in primiparous Holstein cows. 781 5

Neuroendocrine gut and pancreatic tumors are neoplasms that present distinct features from other malignant tumors. Firstly, in most patients, tumor growth is rather slow, and even in advanced metastatic disease, there is very little impairment of the general well-being of the individual, e.g. appetite and weight. Secondly, these tumors are known to produce specific peptide hormones which may be factors in some clinical conditions e.g. carcinoid, Zollinger-Ellison and hypoglycemic syndromes. These conditions can be critical to the patients and can occasionally be lethal. Therefore, the treatment of neuroendocrine tumors must control the clinical symptoms related to hormone over-production and prevent further tumor growth. These two features are not always in parallel. Systemic treatment of neuroendocrine tumors mainly consists of chemotherapy, interferon and somatostatin analog administration. Chemotherapy has been used for at least 30 years; the most effective combination has proved to be streptozotocin with 5-fluorouracil or adriamycin. This combination produces biochemical responses in up to 60% of patients with endocrine pancreatic tumors; the results in carcinoid patients are very poor and response rates are < or = 10%. Alpha-interferon (IFN-alpha) produces biochemical responses in approximately 50% of patients with malignant carcinoid tumors, significant reductions in tumor size in 15% and a further 39% of patients have disease stabilization with no further tumor growth. Somatostatin analogs have only been used clinically within the last 10 years, but produce symptomatic improvement in 70% of cases, biochemical responses in 40-60%, but rarely produce any significant reduction in tumor size. These analogs are particularly useful to control severe clinical symptoms and are the first-line therapy for the management of carcinoid patients both peri- and intra-operatively. Patients with endocrine pancreatic tumors, particularly those with glucagon and vasointestinal peptide-producing tumors, benefit most from this type of treatment. Recently, a combination of IFN-alpha and a somatostatin analog has showed an additive effect of these two drugs. The side effects of streptozotocin and 5-fluorouracil are mainly nausea and vomiting which can be controlled with 5-HT3 receptor blocker therapy. Another significant adverse reaction is impaired renal function. The adverse reactions to IFN-alpha are mainly flu-like symptoms, fatigue, mild impairment of liver and bone marrow function and autoimmune reactions in 15% cases. Somatostatin analog treatment causes a low frequency of adverse reactions, those which do occur include gall stone formation and steatorrhea. Future systemic treatment should be based on increased knowledge of the tumor biology, particularly growth-regulatory mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine tumors of the gastrointestinal tract: systemic treatment. 785 82


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