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)

The mechanisms controlling secretion of glucagon and other pancreatic hormones were studied in a patient affected with multihormone-secreting islet-cell tumor. Fasting glucagon levels (3,000 pg./ml.) rose to 10 ng./ml. following arginine stimulation. While oral glucose load and intravenous glucose infusion did not suppress glucagon secretion, insulin administration induced a prompt depression in glucagon levels. Glucagon, insulin, and gastrin levels were suppressed by somatostatin while calcium infusion caused a paradoxical increase. It is suggested that only some of the stimulation-inhibition mechanisms were conserved in this case of glucagon-secreting pancreatic tumor.
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PMID:Suppression and stimulation mechanisms controlling glucagon secretion in a case of islet-cell tumor producing glucagon, insulin, and gastrin. 0 26

The vicinity of several hormone-producing glands as part of the anatomy of the intestinal tract and the resulting interaction has been confirmed by the discovery of hormonal factors of a specifically gastro-intestinal origin. Today we are mainly interested in the interaction between intermediary metabolism and incretory intestinal function; this is characterized by the joint action of conventional glandular hormones such as insulin and pancreatic glucagon as well as by the incretion of diffuse intestinal organs, hormones such as secretin, pancreozymin, motilin, VIP and GIP. The latter are at present subject of active research with the object of discovering their physiological significance be it as tissue hormones or as humoral agents with a "long distance" impact; their role within pathophysiology is also of interest. GIP ("gastric inhibitory peptide"), apart form acting upon the intestinal tract, also causes a marked rise in insulin production; this GIP possibly is the factor responsible for the difference in glucose tolerance following i. v. or oral administration of glucose, something that scientists have been trying to discover for a long time. We have also endeavored to investigate somatostatin. This substance was originally discovered as a hypothalamic factor with inhibitory action on growth hormone secretion; in the meantime, however, cells containing and possibly also producing somatostatin have also been detected in the intestine and particularly in the islets of Langerhans (D-cells). Since somatostatin inhibits insulin secretion and especially glucagon release as well as the exretory functions of the stomach and of the pancreas, the significance of this hormone possibly is that of a tissue hormone with inhibitory action on adjacent cells. As factor inhibiting both endocrine and exocrine secretory processes it would combine these two complexes. The possible therapeutic significance of somatostatin administration to diabetics would lie in the saving of insulin. A third sector of present-day research deals with the interaction between the calcium metabolism and the hormones involved as well as the intestine. We know that patients suffering from primary hyperparathyroidism are prone to contract stomach ulcers and pancreatitis; patients with a gastrinoma and a hyperfunction of the epithelial bodies suffer from a Zollinger-Ellison-sindrome and this again suggests association with endocrine polyadenomatosis (Wermer syndrome). The inhibitory action of the parathormone antagonist calcitonin on the exocrine functions of the intestinal tract, such as the acid secretion of the stomach and the enzyme secretion of the pancreas, have already given rise to some considerations and experiments relative to treatment. It is to be hoped that because of all the joint observations cited above there will be better intergration of research both from the aspect of gastro-enterology and endocrinology. This might hopefully elucidate some of the unresolved problems ranging from basic research to practical application.
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PMID:[Interaction between gastrointestinal hormones and endocrine regulation]. 0 83

Examination of glucose kinetics, pancreatic alpha and beta cell function, plasma lipids, urinary acidification and calcium excretion has been undertaken in a patient with hereditary fructose intolerance. This case was unusual as it was associated with insulin-requiring diabetes, type IV hyperlipemia, hypercalciuria and renal calculi. He also demonstrated the previously described fructose-induced defect of urine acidification. Glucagon and C-peptide assays showed that the pancreatic alpha cells were stimulated by fructose and that the beta cells did not respond to fructose. It is not known whether the latter was due to his diabetes or to the lack of a beta cell response to this sugar. Primed 14C-glucose infusions were used for the first time to study nonsteady state glucose kinetics in man. They showed that, 24 hours after the last insulin injection and under basal conditions, the glucose concentrations increased because glucose production exceeded glucose utilization. However, after the administration of sorbitol the plasma glucose concentration decreased because glucose production decreased. After the administration of sorbitol there was no change in the metabolic clearance of glucose. This reflects the lack of a peripheral insulin effect and is consistent with the lack of any measurable C-peptide. Glucose utilization also decreased, but this decrease was less than the decrease in glucose production. Because the metabolic clearance of glucose remained unchanged, it was concluded that the change in glucose utilization was solely due to the decrease in glucose concentration. The absence of C-peptide in the plasma indicated that changes in glucose turnover were not related to any changes in endogenous plasma insulin. Furthermore, the plasma glucagon concentration increased and, hence, changes in this hormone could not account for the decrease in glucose production. Therefore, it was concluded that the sorbitol-induced decline in glucose production was due to a direct effect on hepatic metabolism.
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PMID:Studies of glucose turnover and renal function in an unusual case of hereditary fructose intolerance. 1 54

A membrane fraction enriched in parathyroid hormone (PTH)-sensitive adenylate cyclase and sodium and potassium ion-activated (Na+, K+)-ATPase was prepared from bovine kidney. Tritiated PTH binding to this membrane fraction was dependent on both hormone and membrane protein concentration. Both total and specific binding of the hormone decreased significantly after 5 to 10 min of incubation at 22 degrees. PTH binding was highly specific, being sensitive to inhibition only with active forms of unlabeled hormone (native and 1-34 PTH). Specific binding showed a pH optimum of 7.3 to 7.5. Inhibition of binding of tritiated hormone by unlabeled PTH was also highly effective at pH 6.0, but this apparently specific binding was also inhibited by adrenocorticotropic hormone, insulin, glucagon, and vasopressin. Dissociation of bound hormone was demonstrated, and an apparent dissociation constant of 4.6 X 10(-2) min-1 was obtained. Specific binding was eliminated by pretreatment of the membranes with trypsin. The concentration dependence for inhibition of binding with unlabeled PTH was identical to that for activation of adenylate cyclase in this membrane preparation, and binding was also inhibited by concentrations of calcium in the 0.5 to 2 mM range.
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PMID:Binding of tritiated bovine parathyroid hormone to plasma membranes from bovine kidney cortex. 1 29

Besides their well-known actions, glucagon, ACTH, pentagastrin and insulin from the APUD series exert a direct action on the bone calcium content. Incubation with these substances of rat calvaria in vitro yields an evident stimulation of osteolysis with ACTH. Pentagastrin inhibits osteolysis. Glucagon and insulin inhibit parathormone-stimulated osteolysis, with no influence on the spontaneous one. Glucagon, resembling calcitonin, stimulates the 45Ca uptake from the incubation medium. The action of these substances completes the series of hormones influencing bone calcium metabolism, underlining possible interference actions of APUD-type hormones.
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PMID:Effect of "APUD"-type hormones on osteolysis in vitro. 2 23

Addition of 10 micron of the alpha-adrenergic agonist phenylephrine to polymorphonuclear leukocytes suspended in glucose-free Krebs-Ringer bicarbonate buffer (pH 6.7) activated phosphorylase, inactivated glycogen synthase R maximally within 30 s, and resulted in glycogen breakdown. Phenylephrine increased 45Ca efflux relative to control of 45Ca prelabelled cells, but did not affect cyclic adenosine 3',5'-monophosphate (cAMP) concentration. The effects of phenylephrine were blocked by 20 micron phentolamine and were absent in cells incubated at pH 7.4. The same unexplained dependency of extracellular pH was observed with 2.5 nM--2.5 micron glucagon, which activated phosphorylase and inactivated synthase-R, but in addition caused a 30-s burst in cAMP formation. 25 nM glucagon also increased 45Ca efflux. The activation of phosphorylase by phenylephrine and possibly also by glucagon are thought mediated by an increased concentration of cytosolic Ca2+ activating phosphorylase kinase. The effects of 5 micron isoproterenol or 5 micron epinephrine were independent of extracellular pH 6.7 and 7.4 and resulted in a sustained increase in cAMP, an activation of phosphorylase and inactivation of synthase-R within 15 s, and in glycogenolysis. The effects of both compounds were blocked by 10 micron propranolol, whereas 10 micron phentolamine had no effect on the epinephrine action. The efflux of 45Ca was not affected by either isoproterenol or epinephrine. The beta-adrenergic activation of phosphorylase is consistent with the assumption of a covalent modification of phosphorylase kinase by the cAMP dependent protein kinase. Phosphorylation of synthase-R to synthase-D can thus occur independently of increase in cAMP, but the evidence is inconclusive with respect to the cAMP dependent protein kinase also being active in this phosphorylation.
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PMID:Effects of catecholamines and glucagon on glycogen metabolism in human polymorphonuclear leukocytes. 2 35

Left ventricular force-generating capacity was determined in 19 anesthetized dogs with heart failure (HF) from aortocaval fistula. At the time of study all dogs had ascites, edema, and elevated pulmonary wedge pressure. Length-contractile force (CF) curves recorded from the left ventricle (LV) with a modified Walton-Brodie arch indicated that the LV was operating on the ascending limb of the length-CF curve at 62.4 +/- 0.1% Lmax in the normal group and in the HF group at 83.4 +/- 2.7% Lmax. In HF the length-CF curve was depressed when compared to normal and was further depressed when CF in grams was normalized for changes in LV wall thickness and expressed as g/cm2. Additionally, dose-response curves of CF in response to injected norepinephrine, isoproterenol, glucagon, and calcium were depressed when compared to the normal group while the response of heart rate and blood pressure was not different. These findings indicate that volume overload HF is associated with depressed ventricular muscle function and a depressed response to inotropic drugs.
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PMID:Volume overload heart failure: length-tension curves, and response to beta-agonists, Ca2+, and glucagon. 3 75

1. The adenylate cyclase in Trypanosoma brucei is located in the plasma membrane. 2. A partial kinetic analysis of the properties of the enzyme revealed a Km for ATP of 1.75 mM and a Km for Mg2+ of 4mM. 3. At low concentrations, Mg2+ activated the enzyme directly in addition to its effect of lowering the concentration of inhibitory free ATP species. 4. At high concentrations, Mg2+ inhibited the enzyme. Furthermore, the enzyme was inhibited at any Mg2+ concentration if the concentration of ATP exceeded that of Mg2+. 5. The opposing effects of Mg2+ at low and high concentrations would be consistent with more than one binding site for Mg2+ on the enzyme. 6. A study of the patterns of product inhibition revealed little or no effect of 3':5'-cyclic AMP, but a profound inhibition by pyrophosphate, which was competitive with respect to ATP (Ki 0.135 mM). This result suggests that the substrate-binding domain on T. brucei adenylate cyclase interacts mainly with the triphosphate portion of the ATP molecule. 7. The enzyme activity was unaffected by the usual mammalian enzyme effectors glucagon, adrenaline, adenosine, GTP and guanyl-5'-yl imidodiphosphate. 8. The enzyme was not activated by fluoride, instead a powerful inhibition was found. The enzyme was also inhibited by relatively high concentrations of Ca2+ (1 mM).
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PMID:Adenylate cyclase in bloodstream forms of Trypanosoma (Trypanozoon) brucei sp. 3 75

Experiments were performed to determine if catecholamines can regulate control points in the gluconeogenic pathway, such as mitochondrial pyruvate carboxylation and pyruvate kinase activity, via an alpha-adrenergic, adenosine 3':5'-monophosphate-independent mechanism. Of a number of alpha agonists tested, only norepinephrine, epinephrine, and phenylephrine caused an increase in mitochondrial pyruvate metabolism. The effects of catecholamines on pyruvate carboxylation were not attenuated by 1-propranolol which abolishes changes in cyclic nucleotide levels but were blocked by alpha antagonists such as ergotamine, phenoxybenzamine, and phentolamine. Time course experiments demonstrated that the effects of catecholamines on the mitochondria and on carbohydrate metabolism correlated temporally with the concentration of epinephrine in the medium but not with the small changes in adenosine 3':5'-monophosphate. The effects of catecholamines appeared to require extracellular Ca2+ ion. The observation that catecholamines do not increase gluconeogenesis to the same extent as glucagon was not due to a differential effect on mitochondrial CO2 fixation. Rather, catecholamines caused a smaller inhibition of pyruvate kinase activity than did glucagon. The effects of catecholamines on pyruvate kinase also appeared to be mediated by an alpha-adrenergic, adenosine 3':5'-monophosphate-independent mechanism.
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PMID:Regulation of mitochondrial pyruvate carboxylation and gluconeogenesis in rat hepatocytes via an alpha-adrenergic, adenosine 3':5'-monophosphate-independent mechanism. 3 83

The clinical symptomatology of the Zollinger-Ellison syndrome and the pathologic anatomy of gastrinomas are reviewed. Experience with 17 patients with the Zollinger-Ellison syndrome is presented with special reference to stimulation tests (secretin, glucagon, calcium infusion, test meal) and to localization and immunohistologic, ultrastructural, and biochemical findings in gastrinomas. Multiple hormone production by the tumors is frequent. The ultrastructure and the Sephadex G-50 gel filtration patterns of immunoreactive gastrin in sera and tumors are not uniform and are not related to localization of the tumors in the pancreas or duodenum or to the gastrin concentration. Hyperplasia of the pancreatic islets is a frequent finding in gastrinoma patients, suggesting that hypergastrinemia may stimulate islet growth.
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PMID:Pathomorphologic, biochemical, and diagnostic aspects of gastrinomas (Zollinger-Ellison syndrome). 4 19


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