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)

Specific modification of the single lysine residue (Lys-12) in glucagon with O-methylisourea has been effected by blocking the reactivity of the amino terminal histidine with copper, providing a method for obtaining [12-homoarginine]glucagon. It was found that as a side reaction, under the conditions of the modification reaction, Cu(II) catalyzed cleavage of the polypeptide chain between Asp-9 and Tyr-10, and between Lys-12 and Tyr-13. This observation may be of value for development of a sequence-specific peptide cleavage procedure. The dilute solution conformations of glucagon and [12-homoarginine]-glucagon were compared by circular dichroism, fluorescence, phosphorescence, energy transfer, and optical detection of magnetic resonance. The results indicate that conversion of Lys-12 to homoarginine does not alter the helix content the side chain conformation in the vicinity of the tyrosine and tryptophan residues, or the relative distances and orientations between these residues. However, the modification reduces the hormone potency towards activation of lipolysis in isolated rat epididymal fat cells by a factor of seven. We attribute the loss of potency to an interference with a specific interaction between the lysine residue and the fat cell hormone receptor, and not to a change in the solution conformation of the hormone.
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PMID:[12-Homoarginine]glucagon: synthesis and observations on conformation, biological activity, and copper-mediated peptide cleavage. 42 94

Stimulation of the immune system results in a series of metabolic changes that are antagonistic toward growth. Monokines, including interleukin-1, tumor necrosis factor, and interleukin-6, are released from cells of the monocyte-macrophage lineage after recognition of immunogens. They appear to mediate homeorhetic response, which alters the partitioning of dietary nutrients away from growth and skeletal muscle accretion in favor of metabolic processes which support the immune response and disease resistance. These alterations include 1) decreased skeletal muscle accretion due to increased rates of protein degradation and decreased protein synthesis; 2) increased basal metabolic rate resulting in increased energy utilization; 3) use of dietary amino acids for gluconeogenesis and as an energy source instead of for muscle protein accretion; 4) synthesis by the liver of acute phase proteins; 5) redistribution of iron, zinc, and copper within the body due to the hepatic synthesis of metallothionein, ferritin, and ceruloplasmin; (6) impaired accretion of cartilage and bone; and 7) release of hormones such as insulin, glucagon, and corticosterone. These monokines also influence the differentiation of cells. Tumor necrosis factor suppresses the differentiation of myoblasts and adipocytes whereas the chicken monokine myelomonocytic growth factor induces the differentiation of granulocytes.
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PMID:Monokines in growth and development. 171 68

Norepinephrine (NOR) is a potent activator of carbohydrate metabolism in isolated hepatocytes from copper rockfish (Sebastes caurinus), increasing rates of glycogenolysis fourfold with an EC50 of 6.3 nM. Nanomolar concentrations of NOR also enhance gluconeogenesis. Epinephrine (EPI) activates both pathways to a smaller extent; the corresponding EC50 for glycogenolysis is 320 nM. There is no significant difference between the magnitude of glucose production in response to comparable doses of NOR, bovine glucagon, and catfish glucagon-like peptide. Experiments with an adrenergic agonist (isoproterenol) and antagonists (propranolol, prazosin, atenolol) indicate that NOR effects are mediated through beta-adrenoceptors. Catecholamine-activated glycogenolysis measured at 100 nM EPI or NOR is poorly correlated with a 30-50% rise in intracellular cAMP. Glucose production following catecholamine administration is not linear: 50% of the hourly glucose output is released within the first 17 min (NOR) and 5 min (EPI), respectively. During hepatocyte incubation (60 min at 15 degrees), added NOR and EPI (100 nM) were not degraded to any significant extent. In the absence of added hormones, rockfish hepatocytes produce 7.41 +/- 0.89 mumol glucose x g-1 packed cells x hr-1 at 15 degrees, with gluconeogenesis accounting for 35.0% of the total production. The rate of glucose output, which is linear for at least 60 min, is not correlated with the initial hepatocyte glycogen level.
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PMID:Norepinephrine: a potent activator of glycogenolysis and gluconeogenesis in rockfish hepatocytes. 197 May 44

Atrophy of the exocrine pancreas was induced in rats by feeding a copper-deficient diet combined with penicillamine. The treatment resulted in significant decreases in the weights of pancreas and stomach but an increase in the weight of the small intestine compared with control animals receiving the same amount of food. Despite almost total destruction of acinar cells, the content of vasoactive intestinal polypeptide, (VIP) and substance P in the pancreas was not different from controls but the total somatostatin increased by 258% and the glucagon content by 370%. Significant decreases (p less than 0.05) in the concentrations (pmol/g) of VIP, substance P and somatostatin in the small intestine were observed but the total amount (pmol/organ) of the peptides was unchanged. Similarly, an increase (59%) in the concentration of gastric somatostatin in exocrine atrophy was not reflected in a significant difference in the total amount. The content of enteroglucagon in the small intestine was not different in the two groups suggesting that this material was not the trophic influence leading to increased intestinal weight.
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PMID:The effect of pancreatic acinar atrophy upon the concentration of vasoactive intestinal polypeptide, substance P, somatostatin and glucagon in the pancreas and gastrointestinal tract of the rat. 241 Mar 16

The spontaneous diabetic Cohen-rat is one of the few animal models of the diabetes mellitus Type II (NIDDM). A spontaneous diabetic animal line and a diabetes-resistant line originated from a parental lineage by genetic selection with regard to the glucose tolerance on condition of feeding of a saccharose-rich and copper-poor diet. In each case 1000 islets of the diabetes-resistant line were transplanted in 28 animals of the diabetic line. Body weight, blood-sugar concentration, glucosuria, glucose tolerance, and the HbA1 were normalized after the transplantation. The serum levels of insulin and glucagon increased. These results emphasize etiopathogenetic importance of the islets of Langerhans in this animal model.
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PMID:[Islet transplantation in type II diabetes mellitus--model of the spontaneous diabetic Cohen rat]. 250 51

The purpose of this study was to develop a nonenzymatic method of isolating adult islets using atrophied pancreata from copper-deficient rats and to analyze their morphologic characteristics and behavior in culture. This unusual model of isolation was studied because islets remain intact in the course of dietary copper deficiency while the acinar glandular component of the pancreas undergoes selective atrophy and lipomatosis. Small fragments containing islets were readily microdissected from atrophied glands and placed in culture. Within 24 h the fragments congealed into small irregular- to spherical-shaped masses within which the darker profile of islets could be distinguished. Within a period of 3 to 5 d, islet tissue began to bud from the lipocytic mass until by Day 7 spherical aggregates of intact islet tissue separated from the residual fragments. Subsequent to further in vitro treatment, these islets could be maintained as free viable spherical masses if periodically agitated, as attached stationary islets which developed monolayer growth if left undisturbed and as aggregated masses of islet tissue forming megaislets if combined in small groups. Grouped islets treated with actinomycin D and cycloheximide did not exhibit aggregation when incubated with these inhibitors. This suggests that megaislet formation was an active process requiring protein-RNA synthesis rather than passive clumping or aggregation that can accompany metabolically altered or dying islets undergoing cellular shedding and adhesion. Immunohistochemical localization demonstrated that insulin, glucagon, somatostatin, and pancreatic polypeptide-immunoreactive cell types were present within the islets derived from this technique. The cellular topography of these islets was not unlike that described by others for islets cultured from enzymatic isolation. This culture model may serve as a resource for mature, viable islets isolated without mechanical or enzymatic disaggregation which can have attenuating effects on islet function.
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PMID:Nonenzymatic isolation and culture of adult islets from atrophic pancreata of copper-deficient rats: a morphologic analysis. 289 82

Immune responses result in a variety of metabolic adjustments that are mediated by cytokines of leukocytic origin. Of the dozens of cytokines released during an immune response, interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) are the major mediators of intermediary metabolism. These three cytokines act in concert to decrease food intake, increase resting energy expenditure, gluconeogenesis, glucose oxidation, and hepatic synthesis of fatty acids and acute phase proteins, decrease fatty acid uptake by adipocytes and alter the distribution of zinc, iron and copper. Most of these activities result from direct interactions between the cytokine and the responding cells. IL-1, TNF alpha and IL-6 also affect changes in metabolism by changing levels of circulating insulin, glucagon and corticosterone. The nutritional impact of these metabolic changes is dependent upon age. In growing animals, increases in energy expenditure and oxidation of amino acids are balanced by lower needs associated with growth. In adult animals, energy and amino acid requirements are increased by an amount similar to the increased basal metabolic rate and amino acid oxidation. Nutrition also influences the release of cytokines and consequently affects regulation of the immune response. For example, protein deficiency results in decreased IL-1 release and impaired tissue responses to IL-1.
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PMID:Nutritional aspects of leukocytic cytokines. 306 44

The present study determines the effect of glucagon on the behavior of zinc, copper, calcium and magnesium ions in human plasma and urine. Five normal adults were submitted to intravenous infusion of 2.0 mg glucagon over a period of 120 min. A decrease in plasma magnesium and copper was observed with no significant change in urine ion concentrations. We related plasma magnesium mobilization to glucagon, and copper mobilization to plasma variation in free fatty acids and albumin.
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PMID:Metabolic effects of glucagon on plasma and urine zinc, copper, calcium and magnesium levels. 317 77

Anglerfish islet secretory granules have been examined for the presence of an enzyme which could perform C-terminal amidation of glucagon-like peptide II and possibly anglerfish peptide Y. Using [125I]D-Tyr-Val-Gly as substrate, a peptidyl-glycine alpha-amidating monooxygenase (PAM) was detected in islet secretory granule lysates. The enzyme is active between pH 6.0 and 8.5 and exhibits maximal activity near pH 7.0. The islet PAM requires Cu2+, ascorbate, and molecular oxygen for activity. Other divalent metal ions and redox cofactors were tested and found to be inactive in the assay. Even though added Cu2+ and ascorbate are required for detecting islet PAM activity, when these factors were incubated with substrate in the absence of secretory granule lysate, no activity was observed. It was also found that the addition of higher than optimal concentrations of either Cu2+ or ascorbate inhibited amidating activity. The results demonstrate that a PAM is present in secretory granules of anglerfish islet tissue. The characteristics of the islet PAM are similar to those of PAMs identified and characterized in other tissues which produce bioactive C-terminally amidated peptides.
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PMID:Peptidyl-glycine alpha-amidating monooxygenase is present in islet secretory granules of the anglerfish, Lophius americanus. 330 55

This report describes measurements of 50 variables in adult, female, reproductively inactive Vervet monkeys during prolonged nutrition realistic for westernized people. Dietary treatments consisted of an atherogenic Western diet (WD) and a prudent Western diet (PD). Ingredients were normal foods for man and no extra cholesterol was added. Fortification of both diets with vitamin C after cooking was necessary to prevent deficiency. Randomised groups of Vervet monkeys received either the PD or WD for 47 months, while a third group was fed WD for 20 months and then PD for 27 months (WD-PD). Before the dietary treatments nourishment was by a high carbohydrate diet (HCD) and baseline and reference values (RV) apply to this nutritional status. Plasma total cholesterol (mg/dl) was increased from 147 (HCD) to 174 (PD) and 376 (WD). Individual cholesterolaemio response ranged from mild to severe and was stable (PD and WD). Dietary reversal (WD-PD) reduced cholesterolaemia promptly. Statistically significant increases in calcium, zinc and vitamin E and decreased vitamin B6 were associated with the WD relative to the PD (in serum and plasma). Two cholesterol metabolising microsomal enzymes in liver were notably increased and one unchanged (WD). There were no dietary effects on triglycerides, vitamin A and glucose in plasma; insulin, glucagon, electrolytes, copper, magnesium or enzymes reflecting liver, muscle or brain cell damage in serum. Red blood cells, platelets and directly associated parameters increased (WD), haemoglobin was the same and haemoglobin per red cell decreased. Bleeding time was not affected. Bivariate correlations across the diets confirmed that Western nutrition promoted inherent individual susceptibility to cholesterolaemia. There were notable differences from RVs in total cholesterol, calcium, packed cell volume and haemoglobin, which emphasise excesses and deficiencies of the WD and PD.
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PMID:Diets realistic for westernized people significantly effect lipoproteins, calcium, zinc, vitamins C, E, B6 and haematology in vervet monkeys. 363 58


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