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)

Primary cultures of rat liver parenchymal cells maintained as a monolayer in serum-free culture medium were used to investigate the characteristics of zinc accumulation in vitro. Liver parenchymal cells accumulated zinc by a temperature-dependent, saturable process that was inhibited by cyanide, azide, oligomycin, N-ethylmaleimide and iodoacetamide. Cadmium reversibly inhibited zinc accumulation in both serum-free and serum-containing media. Gel filtration chromatographic studies showed that recently accumulated intracellular zinc was present as a low molecular weight complex smaller than metallothionein, the zinc storage protein, but larger than individual amino acids. The quantity of zinc accumulated was affected by preincubation of the cells with various hor?ONES. Dexamethasone, prednisone and prednisolone each increased zinc uptake by 40--50% when either insulin or glucagon was also present. Hydrocortisone, cortisone and sex steroids did not influence zinc accumulation. Removal of the polypeptide hormones from the medium abolished the stimulatory effect of the synthetic glucocorticoid steroid hormones on zinc accumulation.
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PMID:Zinc uptake by isolated rat liver parenchymal cells. 7 27

A 47-year-old white man had a malignant glucagonoma and severe necrolytic migratory erythema. His plasma glucagon levels were markedly elevated at 50 ng/mL and plasma amino acids diminished to 45% of normal. To test the hypothesis that the skin rash associated with a glucagonoma is secondary to an amino acid deficiency, we obtained 2 d of fasting baseline laboratory data from the patient while he consumed his usual diet. He was then given 3 L/d of supplemental intravenous amino acids for 3 d. His plasma amino acid levels increased slightly, and there was some improvement in his skin rash. Immediately thereafter, total parenteral nutrition was administered for 3 d without added zinc or fatty acids. During total parenteral nutrition, 14 of 17 plasma amino acids became normal, and the patient's skin rash rapidly disappeared. These findings suggest that the skin rash associated with a glucagonoma is most likely due to an amino acid deficiency and can be reversed by parenteral nutrition.
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PMID:Amino acid deficiency and the skin rash associated with glucagonoma. 11 95

Adult rats were rendered diabetic by a single iv injection of streptozotocin (70 or 75 mg/kg). In these rats, serum insulin fell to minimal levels during the 48 h following drug treatment, and this was roughly paralleled by a progressive decrease in the ability of the lung to oxidize glucose. The addition of insulin to diabetic rat lung slices in vitro had no restorative effect on the depressed glucose oxidative rate during a 2 h incubation period; however, two daily treatments of the rats with 1 unit of protamine, zinc insulin completely restored lung glucose oxidation rate to normal, without significantly reducing the hyperglycemic state of the rats. An examination of the temporal changes in glucose utilization by the rat lung after acute insulin treatment revealed that the diabetic lung responded directly to serum levels of insulin, whereas the normal lung appeared to be unaffected by serum insulin levels as hihg as 87 ng/ml. The reduced rate of glucose oxidation in the diabetic lung was apparent after perfusion of the lung with glucose-free medium, and was characterized by a significant reduction in Vmax without an alteration in Km. This was attended by a depressed ability of the lung to incorporate [3H]leucine into protein and an increased ability to produce lactate, but hexose monophosphate shunt activity was normal. Specific receptors for insulin have been identified and partially characterized in crude membrane preparations of normal rat lung. The interaction of insulin with these receptors was rapid, reversible, saturable, and was dependent upon time and temperature. The binding of labeled insulin was inhibited by low concentrations of unlabeled insulin and by high concentrations of proinsulin, whereas it was unaffected by the presence of glucagon, gastrin, prolactin, ACTH, or growth hormone in microgram amounts. These observations suggest that insulin regulates the transport and utilization of glucose in the rat lung, and that this tissue contains specific receptors for insulin.
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PMID:Pulmonary insulin responsivitiy: in vivo effects of insulin on the diabetic rat lung and specific insulin binding to lung receptors in normal rats. 14 46

Alloxan diabetic rats maintained on protamine zinc insulin for two weeks were used for these studies. Hepatocytes were isolated from these rats at various time intervals after withdrawal of insulin (0, 48, 72 and 96 hr). Gluconeogenesis with various concentrations of lactate and fructose was studied. Both lactate and fructose stimulated gluconeogenesis and showed progressive increases in glucose production up to 72 hr after the insulin withdrawal. Glucose production decreased at 96 hr. Protein synthesis in isolated hepatocytes from diabetic liver cells, as measured by the incorporation of radioactive isoleucine, valine and phenylalanine into protein, showed a decrease (5- to 6-fold) with time after insulin withdrawal. Glucagon (10(-6)M) alone increased cyclic AMP levels 10-fold in liver cells, in isolated cells from rats maintained on insulin (0 hr) or from rats withdrawn from insulin for 48 hr. The ability of glucagon to elevate cyclic AMP levels in isolated diabetic liver cells decreases 72 hr following insulin withdrawal.
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PMID:Studies on gluconeogenesis, protein synthesis and cyclic AMP levels in isolated hepatocytes from alloxan diabetic rats. 17 99

Subacute cadmium treatment (CdCl2, 1 mg/kg twice daily for 7 days) in rats disturbs glucose homeostasis as shown by hyperglycemia and decreased glucose tolerance associated with suppression of insulin release, enhancement of hepatic gluconeogenic enzymes and decrease in hepatic glycogen content. 2 Exposure to cadmium increases hepatic cyclic adenosine 3',5'-monophosphate (cyclic AMP) and this is accompanied by stimulation of basal, adrenaline- as well as glucagon-stimulated form(s) of adenylate cyclase. 3 In contrast to cadmium, subacute administration of zinc (ZnCl2, 2 mg/kg twice daily for 7 days) fails to alter the activities of hepatic gluconeogenic enzymes, cyclic AMP synthesis, as well as glucose clearance and insulin release in response to a glucose load. 4 Zinc, when administered at the same time as cadmium, prevents the cadmium-induced lesions in both hepatic and pancreatic functions. 5 The results are discussed in relation to the possible mechanisms of cadmium toxicity and to the role of sulphydryl groups in the protection exercised by zinc.
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PMID:Prevention by zinc of cadmium-induced alterations in pancreatic and hepatic functions. 18 49

We treated a two-month-old infant with servere intractable hypoglycemia and nesidioblastosis with continuous glucose infusions (0.75 g per kilogram per hour) via a central venous catheter. Preprandial glucose levels on this regimen were 37+/-2 mg per deciliter (+/-S.E.M.). Basal serum insulin levels were within normal fasting levels for this age group but inappropriately elevated for the blood glucose levels. The beta cells were exquisitely sensitive to infusions of synthetic cyclic somatostatin, with a dose-dependent rise in blood glucose and concomitant suppression of serum insulin levels. There was only minimal suppression of plasma glucagon levels. Single subcutaneous injections of 50 microng of protamine zinc somatostatin raised preprandial blood glucose levels to 83+/-3 mg per deciliter for four to five days although preprandial hormone levels were unchanged. These findings indicate that hypoglycemia of infancy is a hyperinsulin state with abnormal basal regulation of insulin secretion.
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PMID:Hypoglycemia of infancy and nesidioblastosis. Studies with somatostatin. 19 7

To investigate the role of hepatic glucagon receptors in the hypersensitivity to glucagon observed in insulin-deprived diabetics, liver plasma membranes were prepared from control rats and from streptozotocin-induced diabetic rats some of whom were treated with high-dose and low-dose insulin. The untreated diabetic animals exhibited hyperglycemia, weight loss, hypoinsulinemia, and hyperglucagonemia. High-dose insulin treatment (2 U Protamine-zinc-insulin/100 g per day) resulted in normoglycemia, normal weight gain, mild hyperinsulinemia, and return of glucagon levels toward base line. The low-dose (1 U protamine-zinc-insulin/100 g per day) insulin-treated diabetic group demonstrated chemical changes intermediate between the untreated and the high-dose insulin-treated animals. In liver plasma membranes from the untreated diabetic rats, specific binding of (125)I-glucagon was increased by 95%. Analysis of binding data suggested that the changes in glucagon binding were a consequence of alterations in binding capacity rather than changes in binding affinity. Furthermore, in the untreated diabetic rats, both basal and glucagon (2 muM)-stimulated adenylate cyclase activity were twofold higher than in controls. In the high-dose insulin-treated diabetic rats, glucagon binding and basal and glucagon-stimulated adenylate cyclase activity were normalized to control values, whereas low-dose insulin treatment resulted in changes intermediate between control and untreated diabetic rats. In contrast to glucagon-stimulated adenylate cyclase activity, fluoride-stimulated adenylate cyclase activity was similar in all groups of rats. Liver plasma membranes from untreated and insulin-treated diabetic animals degraded (125)I-glucagon to the same extent as control rats. The specific binding of (125)I-insulin in the untreated diabetic animals was 40% higher than in control rats. In low-dose insulin-treated diabetic rats, insulin binding was not significantly different from that of control rats, whereas in the high-dose insulin-treated group in whom plasma insulin was 70% above control levels, insulin binding was 30% lower than in control rats. These findings suggest that alterations in glucagon receptors may contribute to the augmented glycemic and ketonemic response to glucagon observed in insulin-deprived diabetics.
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PMID:Glucagon binding and adenylate cyclase activity in liver membranes from untreated and insulin-treated diabetic rats. 700 82

The results of a double-blind trial of glucagon in 69 patients with acute pancreatitis are reported. In a subgroup of 59 patients statistical analysis showed no significant differences between the glucagon-treated (n = 29; 2 X 5 mg protamine-zinc glucagon intramuscularly per day) and the placebo-treated (n = 30) subjects for the following data: duration of pain left spontaneously and induced by palpation, amounts of analgesics and antispasmodics required by the patients, duration of hospital stay, amylase activities in serum and 24 hour urine collections. Mortality rates did not differ significantly between the glucagon-treated and the placebo-treated subjects in the total group of 69 patients and in the two subgroups of patients who were treated conservatively (n = 59) and those who underwent laparotomy because of severe peritonitis (n = 10). From the results of this study it is concluded that favourable effects of glucagon upon the course of acute pancreatitis--if they do exist--are not significant.
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PMID:Glucagon therapy in acute pancreatitis. Report of a double-blind trial. 34 59

Foetal rat pancreatic rudiments explanted on day 14 of gestation were grown for 6 days in organ culture in medium containing glucose (5.5(1G) or 16.5(3G)mmol/l) and amino acids at the 'physiological' (1AA) or seven times the 'physiological' (7AA) concentration. Cultures were also performed in medium to which zinc sulphate had been added at 10(-7) to 10(-5) mol/l concentration. At the end of the period of culture the diameters of insulin, glucagon and zymogen granule profiles in the rudiments were compared with those in normal 20-day foetal pancreas by quantitative morphology. The beta cell volume, the number of granules per beta cell, the insulin granular volume fraction and the area of insulin granule core and halo were also measured under selected experimental conditions. Zymogen granule profiles were largest in vivo, intermediate in diameter when grown in 1G x 7AA medium and smallest in 1G x 1AA medium. The mean diameter of glucagon granule profiles remained constant for growth in vivo, in 1G x 7AA medium. Insulin granule profiles were largest in 1G x 1AA medium or in 1G x 7AA medium, smallest in 3G x 1AA mdeium and of intermediate diameter in vivo. Amino-acid enrichment increased the diameter of insulin granules and glucose enrichment decreased it. The addition of zinc to the culture medium had no effect on insulin granule diameter. In 1G x 7AA cultures the beta cells were of similar size to those in vivo, but there were 29% fewer insulin granules per cell. The increased size of the insulin granules in 1G x 7AA cultures resulted in the insulin granule volume fraction in 1G x 7AA being 17.6 compared with 10.8% in vivo. Insulin granule cores were made larger by amino-acid enrichment of the culture medium but they were unaffected by glucose. The haloes were larger in 7AA medium and smaller in 3G medium. Glucose and amino-acid enrichment had a significant interaction on halo area, the mean area in 3G x 7AA medium being less than would have been expected from the summation of the effects of the two conditions.
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PMID:Effects of glucose and amino acids on insulin, glucagon and zymogen granule size of foetal rat pancreas grown in organ culture. 38 71

In contrast to intravenously-administered crystallene glucagon, which acts for 20 minutes only, the depot form, zinc protamine glucagon, shows a prolonged haemodynamic action. Fourteen patients with pre-existing heart failure received a single dose of 20 mg Zn protamine glucagon intramuscularly. The stroke volume and cardiac output were increased, whereas the mean and end-diastolic pulmonary pressure were decreased, indicating a positive inotropic action of the administered drug. Heart rate and mean arterial pressure remained almost unchanged. The haemodynamic changes started 60 minutes after intramuscular administration of the drug, reached a maximum effect at 3 hours and started to decrease after the fourth hour. Zn protamine glucagon can, therefore, be considered a beneficial drug in the treatment of digitalis-resistant heart failure on the basis of its long duration of action and easy route of administration.
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PMID:[Haemodynamic effects of depot zinc protamine glucagon in heart failure (author's transl)]. 43 80


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