Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of zinc on serum glucose, insulin and glucagon as well as liver glycogen was investigated in normal, adrenalectomized (ADX), and diabetic rats. Serum glucose was significantly elevated within 15 minutes after intraperitoneal administration of zinc (25 mumol) but returned to normal limits within 4 hours. Similar effects on serum glucose were noted with orally administered zinc. Significant depletion of hepatic glycogen in zinc-treated rats suggests glycogenolysis was responsible at least in part for the increased blood glucose. Adrenalectomy completely eliminated the hyperglycemic response to this metal, whereas adrenergic blockade with phenoxybenzamine and propranolol was effective in preventing hyperglycemia. The hyperglycemic response to zinc was not eliminated in diabetic rats. Administration of dexamethasone, alone or in combination with zinc, was unable to change serum glucose concentrations in ADX rats. Plasma glucagon was significantly elevated within 15 minutes but was reduced 6 hours after zinc treatment. Insulin was significantly depressed within 30 minutes after administration of zinc and eventually increased over controls by 4 hours after treatment. These data suggest that the hyperglycemic response to zinc depends on a mechanism, requiring an intact adrenal gland, which acts to produce a rapid alteration in blood glucose.
 ...
PMID:Hyperglycemic action of zinc in rats. 634 23

A further characterization of endotoxin-induced changes in zinc metabolism provided insight into the possible mediation processes involved. Endotoxin reduced serum zinc levels while elevating zinc associated with hepatic metallothionein (Zn-MT) in control, fasted, and zinc-depleted rats. Unlike zinc, copper in the serum and that associated with metallothionein showed little response to endotoxin. In vitro translation of liver mRNA demonstrated that metallothionein mRNA levels were increased after endotoxin administration to either control or zinc-depleted rats. Cycloheximide fully blocked endotoxin-induced alterations in serum and metallothionein zinc, but actinomycin D was only partially inhibitory. Glucagon might act as the primary mediator for these actinomycin D-insensitive changes. Glucocorticoids might be responsible for the remaining alterations in zinc metabolism because dexamethasone increased 65Zn accumulation in cultured hepatocytes, whereas endotoxin did not. In endotoxin-treated rats, the kidney as well as liver showed increases in metallothionein-zinc and metallothionein-mRNA. Virtually all the effects of endotoxin were mimicked by leukocytic endogenous mediator, implying that it probably represents the initial mediator of endotoxin action on zinc metabolism.
 ...
PMID:Mediation of endotoxin-induced changes in zinc metabolism in rats. 638 45

In red cell lysates, three soluble proteases hydrolyze insulin at pH 8.5. One of these enzymes was purified to homogeneity by conventional chromatographic techniques. It appears to be a metalloprotease since it is inhibited by EDTA, o-phenanthroline, and 8-hydroxyquinoline, the metal-depleted enzyme can be reactivated by micromolar levels of Zn2+, Co2+, or Mn2+, and it is not inhibited by reagents specific for carboxyl, serine or thiol proteases. This enzyme has an apparent molecular weight of 300,000 +/- 25,000, and electrophoresis in sodium dodecyl sulfate indicates a single band with an Mr = 115,000 +/- 10,000. End group analysis and automated Edman degradation of the products of proteolysis showed that it is an endoprotease which cleaves on the NH2-terminal side of large hydrophobic amino acids. Although various small polypeptides with Mr = 2300-3500 are hydrolyzed (e.g. insulin chains, glucagon, and calcitonin), a variety of larger proteins are not degraded (e.g. casein and globin). The latter proteins, however, are converted to substrates for the metalloprotease by digestion with the ATP-stimulated endoprotease from erythrocytes. Thus, the metalloprotease may play a role in the ATP-dependent pathway for degrading proteins with abnormal structures and could account in part for the o-phenanthroline sensitivity of this process. A similar enzyme is found in humans, rabbits, and rats and is cytosolic in all tissues which have been examined including erythrocytes, reticulocytes, liver, kidney, brain, and skeletal muscle.
 ...
PMID:A high molecular weight metalloendoprotease from the cytosol of mammalian cells. 640 23

Streptozotocin-induced diabetes produced a significant rise in rat serum and liver triacylglycerol content and hepatic triacylglycerol biosynthesis measured in vivo. Microsomes, isolated from the livers of streptozotocin-exposed animals (2-72h), exhibited an increased capacity to incorporate sn-[1,3-(14)C]glycerol 3-phosphate into neutral lipid (diacylglycerol and triacylglycerol) in the presence of ATP, CoA and palmitate. The streptozotocin-induced elevation of microsomal neutral lipid production was accompanied by a corresponding rise in the activity of microsomal phosphatidate phosphohydrolase (4-fold after 72 h of streptozotocin exposure). Diabetic-dependent increases in acylglycerol formation, phosphatidate phosphohydrolase activity and serum triacylglycerol and fatty acid levels were reversed by administering insulin (10 units protamine zinc/kg) at 16-h intervals (three separate doses( beginning 24 h after streptozotocin exposure. However, the diabetic-related rise in hepatic triacylglycerol content was only partially corrected by insulin administration. Streptozotocin-relate increases in liver triacylglycerol biosynthesis and phosphatidate phosphohydrolase activity we associated with alterations in plasma factors, since homogenates of hepatocyte monolayers exposed (18h) to plasma isolated from diabetic (72 h exposure to streptozotocin) animals exhibit an increased capacity to incorporate sn-[1,3-(14)C]glycerol 3-phosphate into triacylglycerol compared to homogenates of cells exposed to plasma from control (non-fasted) animals. The importance of these plasma factors in altering hepatic acylglycerol formation was also supported by the observation that hepatocyte monolayers exposed to a mixture of plasma isolated from normal (non-fasted) animals and plasma components elevated in diabetes (glucagon, glucose, oleate and ketones) showed increases in triacylglycerol formation which were similar to those produced by exposure to diabetic plasma. Additional studies demonstrated that fatty acids (oleate) appeared to be the agent primarily responsible for the diabetic plasma-induced rise in monolayer triacylglycerol biosynthesis and phosphatidate phosphohydrolase activity.
 ...
PMID:The acute effects of streptozotocin-induced diabetes on rat liver glycerolipid biosynthesis. 645

Rat hepatic zinc thionein levels can be modulated by a variety of external and internal stimuli. Metals, such as zinc or copper, induce levels 20 to 50 fold over controls. Catecholamines can increase levels 10 to 20 fold, while glucocorticoids, such as dexamethasone, can increase levels modestly by 2-6 fold. We have investigated the ability of additional hormones, which have receptors on hepatocytes, to modulate the levels of hepatic zinc thionein. Glucagon, angiotensin II, and Arg-vasopressin were administered intravenously and intraperitoneally, one time and three times, over an 11 hour period. Zinc thionein levels in rat liver were increased 1.7 to 5.6 fold by glucagon and 1.7 to 3.6 fold by angiotensin II, but not at all by Arg-vasopressin, as compared to appropriate controls. Glucagon and angiotensin II, when administered in vivo, can modulate zinc thionein levels in rat liver to an extent similar to glucocorticoids. Hepatic zinc thionein levels must now be recognized to be affected in vivo by metals, glucocorticoids, catecholamines, and polypeptide hormones.
 ...
PMID:Effects of glucagon, Arg-vasopressin, and angiotensin II on rat hepatic zinc thionein levels. 651 26

Is is well known from laboratory investigations and acute intervention studies that glucagon is involved in lipid metabolism. The present study was undertaken in order to evaluate a possible sustained effect of zinc-protamin-glucagon in moderately hyperlipidaemic patients. 4 patients were investigated after an acute bolus dose of glucagon 5 mg intravenously and 16 patients were given zinc-protamin-glucagon 5 mg subcutaneously, b.i.d. for 5 days. A similar degree of decrease of plasma cholesterol and triglycerides was obtained in the acute and chronic study, while the increase in fasting blood sugar and plasma insulin seen in the acute study was not present after 5 days treatment. The effect on plasma triglycerides was much more variable than the effect on plasma cholesterol. Five days after treatment the lipid concentrations had returned to the pretreatment values. The effect could not be predicted from the pretreatment lipid concentrations, neither by the type of hyperlipidaemia present. The decrease in plasma cholesterol and triglycerides were not correlated. The drug might prove useful in the long term research of lipid metabolism and the various complex hormonal interactions.
 ...
PMID:Sustained effect of zinc-protamin-glucagon in hyperlipidaemic patients. 663 8

The influence of a maternal dietary deficiency of zinc, or food restriction on the content and in vitro secretion of pancreatic hormones was measured in rat fetuses on day 19 of gestation. Pregnant Sprague-Dawley rats were fed a zinc-deficient diet (0.4 +/- 0.1 ppm zinc) ad libitum or a zinc-supplemented control diet (100 ppm zinc) either ad libitum or with restricted intake. The insulin content of the fetal pancreas was lower in fetuses from rats subjected to zinc deprivation or to food restriction than in controls. The lower insulin content of fetal pancreata from zinc-deficient rats was related to a lower than normal proportion of insulin-containing beta cells. The lower insulin content of fetal pancreata from rats subjected to food restriction was related to a less than normal amount of insulin per beta cell. Glucagon concentration in the fetal pancreas was lower than normal in response to zinc deficiency but not to food restriction. Fetal hormone release in vitro was also influenced by the maternal diet. The rate of insulin secretion in vitro was normal in fetuses from zinc-deficient rats, but was accelerated in those from females subjected to calorie restriction. The rate of glucagon secretion in vitro was lower than normal in the pancreata of zinc-deficient fetuses. We conclude that insulin and glucagon levels in the fetus were affected by maternal zinc deficiency and, to a lesser extent, by calorie restriction.
 ...
PMID:Effect of maternal zinc deficiency of food restriction on rat fetal pancreas. 2. Insulin and glucagon. 701 96

Twenty patients were changed from a single daily injection of beef insulin (a mixture of soluble and protamine zinc insulin) to two daily injections (mixtures of soluble and isophane insulins). This was associated with a reduction, one month later, in the concentration of glycosylated haemoglobin (HbA1) and in the degree of late evening glycosuria. A reduction was shown 6 months later in antibody binding of beef and pork insulin by serum. Subsequent conversion to a twice daily regime of highly purified pork insulin was not associated with further improvement in diabetic control, but was associated after 1 month with a reduction in daily insulin dose, and after 5 months with a further reduction in antibody binding of beef and pork insulin by serum. Patients failing to show a C-peptide response to intravenous glucagon had a fall in HbA1 after conversion from a once to a twice daily insulin regime, which correlated inversely with insulin antibody binding estimated at the beginning of the study.
 ...
PMID:Diabetic control in patients treated with once or twice-daily insulin injections, including a comparison of conventional beef and highly purified pork insulins. 702 52

Diabetic control, assessed by measuring the concentration in venous blood of total glycosylated haemoglobin (HbA1), endogenous insulin secretion, as estimated by the C-peptide response (delta C-P) to intravenous glucagon, and serum beef insulin antibody binding were measured in 50 juvenile onset insulin dependent diabetics (IDDM) receiving a single daily injection of soluble and protamine zinc insulin. The delta C-P correlated inversely with duration of diabetes (tau = -0.27, p less than 0.01) and daily insulin requirement (tau = -0.22, p less than 0.05) in the 50 IDDM studied of whom 28 exhibited a measurable delta C-P. In C-peptide nonresponders, but not in the C-peptide responders, and inverse regression (t = 2.19, p less than 0.05) was observed between beef insulin antibody and HbA1. In the 25 IDDM having the lowest insulin antibody binding, and inverse correlation (tau = 0.36, p less than 0.02) was observed between delta CP and HbA1, which was not found (tau = 0.05) in the remaining 25 IDDM who had the highest insulin antibody binding. These findings suggest that, in the absence of endogenous insulin secretion, diabetic control in IDDM receiving a single daily injection of conventional beef insulin is better in patients with high beef insulin antibody binding. Conversely, in patients with low beef insulin antibody binding, diabetic control appears to be better in those with persisting endogenous insulin secretion.
 ...
PMID:Relationship of glycosylated haemoglobin to C-peptide secretory status and antibody binding of insulin in insulin-dependent diabetes. 703 Aug 98

Triacylglycerol lipase activities of homogenates and subcellular fractions of rat liver were measured under optimal conditions at pH 7.5 using emulsified tri[1-14C]oleoylglycerol as substrate. Twenty-four hr after administration of streptozotocin, hepatic alkaline lipase activity was 39% of normal, and this lower level of activity was observed at 72 hr and 7 days, after streptozotocin injection. After 24 hr of starvation, lipase activity also was significantly lower (35%) than normal. Insulin (35 U regular/kg body weight) had no acute (90 min) effect on the hepatic lipase activity of either normal or diabetic rats. Chronic insulin administration (4 subcutaneous injections of 10 U protamine zinc insulin/kg at 16-hr intervals) to normal rats provoked a 40% increase in hepatic lipase activity. Diabetic rats given the same insulin treatment showed lipase activity that was significantly higher (155%) than normal. Lipase activity fell to 65% of normal when insulin was withheld (32 hr) from diabetic rats given chronic insulin therapy. Intracardial injection of glucagon (1 mg/kg) into normal rats had no acute (30 min) effect on hepatic alkaline lipase activity. Hepatic alkaline lipase activity varied independently from the concentrations of either glucose or triacylglycerol in the plasma. However, there was an apparent negative correlation between this lipase activity and the concentration of fatty acids in the plasma; lipase activity was highest when fatty acid concentrations were lowest, and lowest when fatty acid concentrations were elevated. From these data we conclude: 1) changes in hepatic alkaline lipase activity ware provoked by chronic, but not acute, alteration of the hormonal and metabolic status of the rat, and 2) changes in hepatic alkaline lipase activity may be mediated through changes in the levels of circulating fatty acids presented to the liver, but the effect is not an immediate one.
 ...
PMID:Hepatic triacylglycerol lipase activities after induction of diabetes and administration of insulin or glucagon. 704 62


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>