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)

A number of hemodynamic, pharmacologic and metabolic interventions were found to change the extent of acute ischemic injury of the myocardium and subsequent necrosis following experimental coronary artery occlusion. Reduction in myocardial damage occurred by decreasing myocardial oxygen demands (beta-adrenergic blocking agents, intra-aortic balloon counterpulsation, external counterpulsation, nitroglycerin, decreasing afterload in hypertensive patients, inhibition of lipolysis, and digitalis in the failing heart); by increasing myocardial oxygen supply either directly (coronary artery reperfusion or elevating arterial pO2), or through collateral vessels (elevation of coronary perfusion pressure by alpha-adrenergic agonists, intra-aortic balloon counterpulsation); or by increasing plasma osmolality (mannitol, hypertonic glucose); presumably by augmenting anaerobic metabolism (glucose-insulin-potassium, hypertonic glucose); by enhancing transport to the ischemic zone of substrates utilized in energy production (hyaluronidase); by protecting against autolytic and heterolytic damage (hydrocortisone, cobra venom factor, aprotinin). Augmentation of myocardial ischemic damage occurred as a consequence of increasing myocardial oxygen requirements (isoproterenol, glucagon, ouabain, bretylium tosylate, tachycardia); by decreasing myocardial oxygen supply either directly (hypoxia, anemia) or through reduction of collateral flow (hemorrhagic hypotension, minoxidil) or by decreasing substrate availability glycemia). Pilot studies have been carried out in patients with hyaluronidase, nitroglycerin, intra-aortic balloon counterpulsation, beta-blocking agents and Arfonad and have shown that these interventions may also reduce myocardial damage, suggesting that the concept of reduction in infarct size following coronary occlusion is applicable clinically.
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PMID:Effects of metabolic and pharmacologic interventions on myocardial infarct size following coronary occlusion. 0 95

Exposure of hamster pancreatic islets to hyaluronidase during isolation by means of collagenase inhibits the insulinotropic action of several chemically different sulfonylureas, leucine, and glucagon without affecting glucose-stimulated insulin secretion. This inhibition is reversible for tolbutamide and leucine but irreversible for glucagon. Hyaluronidase inhibits reversibly the insulinotropic action of tolbutamide without affecting that of glucose also in mouse and rat isolated pancreatic islets . These findings suggest the existence of functionally related pancreatic beta cell receptors for tolbutamide and leucine different from those for glucose and glucagon and illustrate the potential usefulness of hyaluronidase as an enzymatic probe applicable toward investigating the cellular mechanism of action of key insulinotropic agents.
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PMID:Hyaluronidase-induced inhibition of the insulinotropic action of sulfonylureas, leucine, and glucagon in rodent isolated pancreatic islets. 17 48

A number of enzymatic methods have been developed to prepare hepatocytes using collagenase and hyaluronidase. However, best cell preparations are obtained by using only low concentrations of collagenase and exposing the liver to the enzyme for a very short period of time. These isolated cells with intact cell membranes and large numbers of microvilli on the cell surface respond to hormones at physiological concentrations suggesting that these microvilli contain hormone receptors. In addition, high glycogen content is essential to maintain the in vivo metabolic characteristics of the hepatocytes suggesting that intracellular glycogen plays an important role in the hormonal regulation of metabolism in hepatocytes. Studies with glucagon and insulin on carbohydrate metabolism show that the molar ratios of these hormones control gluconeogenesis and glycogenolysis. Furthermore, in vitro addition of insulin stimulates glycogen synthesis and activates glycogen synthase. Insulin also stimulates protein synthesis in cells containing high glycogen and maintains more normal parallel strands of polyribosomes. Studies with isolated hepatocytes from diabetic, hypophysectomized and adrenalectomized animals show a reduced glucagon response to glycogenolysis. This lack of glucagon response was not due to reduction in glycogen levels. Other hormones such as somatostatin and parathyroid also give rise to alterations in carbohydrate metabolism in isolated hepatocytes.
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PMID:Studies of hormonal regulation of metabolism using isolated hepatocytes. 19 66

A number of hemodynamic, pharmacologic, and metabolic interventions were found to change the extent of acute ischemic injury of the myocardium and subsequent necrosis following experimental coronary artery occlusion. Reduction in myocardial damage occurred by decreasing myocardial oxygen demands (beta-adrenergic blocking agents, intra-aortic balloon counterpulsation, nitroglycerin, decreasing afterload in hypertensive patients, inhibition of lipolysis, and digitalis in the failing heart); by increasing myocardial oxygen supply either directly (coronary artery reperfusion or elevating arterial pO2), or through collateral vessels (evevation of coronary perfusion pressure by alpha adrenergic agonists, intra-aortic balloon counterpulsation); or by increasing plasma osmolality (manitol, hypertonic glucose); presumably by augmenting anaerobi metabolism (glucose-insulin-potassium, hypertonic glucoxe insulin potassium, hypertonic glucose); by enhancing transport to the ischemic zone of substrates utilized in energy production (hyaluronidase); by protecting against autolytic and heterolytic damage (hydrocortisone, cobra venom factor, aprotinin). Augmentation of myocardial ischemic damage occurred as a consequence of increasing myocardial oxygen requirements (isoproterenol, glucagon, ouabain, bretylium tosylate, tachycardia); by decreasing myocardial oxygen supply either directly (hypoxia, anemia), through reduction of collateral flow (hemorrhagic hypotension, minoxidil), or by decreasing substrate availability (hypoglycemia). Pilot studies have been carried out in patients with hyaluronidase, nitroglycerin intra-aortic balloon counterpulsation, beta-blocking agents and Arfonad and have shown that these interventions may also reduce myocardial damage, which suggests that the concept of reduction in infarct size following coronary occlusion is applicable clinically.
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PMID:Effects of metabolic and pharmacologic interventions on myocardial infarct size following coronary occlusion. 76 15

Isolation and culture techniques for hepatocytes from whole livers of the cynomolgus monkey, Macaca fascicularis, are described. Hepatocytes were isolated by two-step perfusion of livers, using collagenase with hyaluronidase; fructose and trypsin inhibitor were included to reduce cell loss. Yields from a single liver average 4 X 10(9) cells with viabilities of 90.8 +/- 5.7%. Cells, plated on collagen substrates, were assessed for changes in morphology and various marker enzyme activities over a period of 7 d in culture. Cells exhibited a morphology similar to that observed for this species in vivo; little change in attached and spread cells was observed over the length of time monitored. Enzyme activities for catalase, succinate dehydrogenase, and tyrosine aminotransferase were observed to decrease significantly (though considerable activity remained), whereas acid phosphatase and 5'-nucleotide phosphodiesterase remained unchanged. Activity of cytochrome P-450 reductase was observed to increase slightly for the first 2 d, then decrease to about 60% of initial levels. Activity of alpha-mannosidase was stable for 4 d but was observed to be increased at Day 7. Cells were observed to retain metabolic responsiveness, demonstrated by glucose production by both gluconeogenesis and glycogenolysis in response to glucagon stimulation. The monkey hepatocytes obtained by methods described here thus retain hepatocellular morphology and activity through at least 1 wk in culture without medium or culture modification.
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PMID:Isolation and culture of hepatocytes from the cynomolgus monkey (Macaca fascicularis). 197 77

GST activities against 1-Chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzene (DCNB) were measured in isolated and cultured adult rat hepatocytes. Within 24 h in culture, both GST activities decreased to about 70% and either stabilized at this level (CDNB) or recovered (DCNB) to the initial level. Use of hyaluronidase in addition to collagenase during the isolation of the cells strongly reduced both activities and its stimulation by various drugs for up to 168 h. The hormones insulin, glucagon, triiodothyronine, estradiol, testosterone, and progesterone did not affect GST activity, while dexamethasone showed some interference. In the presence of dexamethasone the activity against CDNB was mainly stimulated by the combination of methylcholanthrene (MC) and phenobarbital (PB) to about 260% within 168 h. The activity against DCNB was stimulated predominantly by MC alone reaching 170% after 168 h. Quantification of the GST subunits Ya, Yb1 and Yp by an ELISA technique revealed a strong decrease of Ya, a transient increase of Yb1 after 24 h followed by a moderate decrease, and a stable low level of the transformation marker Yp during cultivation. The level of Ya was markedly induced by PB, particularly in combination with MC. The level of Yb1 was equally induced by MC or PB with no synergistic effect. Yp was not affected by these drugs. None of the hormones affected the level of these GST subunits. These results indicate that the physiological type of regulation of the GSTs is maintained during primary culture and no signs of dedifferentiation or transformation are observed. Furthermore, they demonstrate that the interaction of drugs and hormones and their inducing potential can be efficiently studied in the cultured hepatocytes.
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PMID:Influence of hormones and drugs on glutathione-S-transferase levels in primary culture of adult rat hepatocytes. 208 92

1. The effect of vasoactive intestinal polypeptide (VIP) upon adenylate cyclase activity was determined in purified cortical basolateral membranes and in glomeruli and tubular elements obtained from rabbit kidney. 2. In purified basolateral membranes prepared from cortex, 1 microM-VIP consistently stimulated adenylate cyclase activity above basal levels (1.55 +/- 0.09-fold (mean +/- S.E. of mean), n = 10 animals). Half-maximal stimulation was observed at 17 +/- 11 nM-VIP (S.D., n = 9). 3. Related peptides, e.g. secretin, glucagon, gastric inhibitory peptide, human pancreatic growth hormone releasing factor, and peptide having N-terminal histidine and C-terminal isoleucine amide (PHI), were without effect or gave lower stimulations of adenylate cyclase activity when tested at 1 microM. 4. Significant VIP degradation was observed under the assay conditions used but this did not substantially alter the response or selectivity to VIP. 5. In separate preparations of isolated glomeruli and proximal tubules addition of 1 microM-VIP resulted in a 3.3 +/- 1.1-fold (S.D., n = 3) and 2.2 +/- 1.0-fold (S.D., n = 3) stimulation (respectively) of adenylate cyclase activity. 6. In isolated medullary tubule suspensions, isolated by collagenase-hyaluronidase digestion of outer (red) medulla, and in thick ascending-limb-enriched preparations prepared by Percoll density gradient fractionation, 1 microM-VIP significantly increased adenylate cyclase activity by 2.4 +/- 0.6-fold (S.D., n = 3) and 2.1 +/- 0.7-fold (S.D., n = 3) respectively. 7. A possible role for VIP in the regulation of renal function in the rabbit is discussed in relation to the occurrence of VIP stimulation of adenylate cyclase activity in several renal cellular elements.
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PMID:Vasoactive intestinal polypeptide regulation of rabbit renal adenylate cyclase activity in vitro. 365 72

The neuropeptide galanin is widely distributed in the gastrointestinal tract and exerts several inhibitory effects, especially on intestinal motility and on insulin release from pancreatic beta-cells. The presence of galanin fibres not only in the myenteric and submucosal plexus but also in the mucosa, prompted us to investigate the regulatory role of galanin, and its mechanism of action, on the secretion of the insulinotropic hormone glucagon-like peptide-1 (GLP-1). Rat ileal cells were dispersed through mechanical vibration followed by moderate exposure to hyaluronidase, DNase I and EDTA, and enriched for L-cells by counterflow elutriation. A 6- to 7-fold enrichment in GLP-1 cell content was registered after elutriation, as compared with the crude cell preparation (929 +/- 81 vs 138 +/- 14 fmol/10(6) cells). L-cells then accounted for 4-5% of the total cell population. Bombesin induced a time-(15-240 min) and dose- (0.1 nM-1 microM) dependent release of GLP-1. Glucose-dependent insulinotropic peptide (GIP, 100 nM), forskolin (10 microM) and the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA, 1 microM) each stimulated GLP-1 secretion over a 1-h incubation period. Galanin (0.01-100 nM) induced a dose-dependent inhibition of bombesin- and of GIP-stimulated GLP-1 release (mean inhibition of 90% with 100 nM galanin). Galanin also dose-dependently inhibited forskolin-induced GLP-1 secretion (74% of inhibition with 100 nM galanin), but not TPA-stimulated hormone release. Pretreatment of cells with 200 ng/ml pertussis toxin for 3 h, or incubation with the ATP-sensitive K+ channel blocker disopyramide (200 microM), prevented the inhibition by galanin of bombesin- and GIP-stimulated GLP-1 secretion. These studies indicate that intestinal secretion of GLP-1 is negatively controlled by galanin, that acts through receptors coupled to pertussis toxin-sensitive G protein and involves ATP-dependent K+ channels.
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PMID:Galanin inhibits glucagon-like peptide-1 secretion through pertussis toxin-sensitive G protein and ATP-dependent potassium channels in rat ileal L-cells. 961 55

Before the 2009 Biologics Price Competition and Innovation Act that enabled the U.S. Federal Drug Administration (FDA) to create the 351(k) Biologic License Application-an abbreviated biosimilar approval process, FDA approved follow-on biomolecule products such as beta-interferon, glucagon, hyaluronidase, and somatropin (human growth hormone) under varying and evolving rules. With the 351(k) Biologic License Application biosimilar approval process in place, currently, there are 4 (licensed in 2015-2016) biosimilars available, namely Neupogen (filgrastim; $1 B/y), Humira (adalumumab; $14.2 B/y), Enbrel (etanercept; $8.7 B/y), and Remicade (infliximab; $6.5 B/y). With well-established product market capitalization of these and other top income producers-such as Rituxan (rituximab; $6.8 B/y), Herceptin (trastuzumab; $6.5 B/y), and Avastin (bevacizumab; $5.8 B/y), and a price differential of 15%-30% compared to branded products, there is an intense interest in development of biosimilars by established pharmaceutical companies. Currently, there are 160 biosimilar candidates in clinical studies, many of which are sponsored by large pharmaceutical companies known for product innovation. This trend will likely continue. Additional information on a biomolecule platform is presented in the Journal of Pharmaceutical Sciences Drug Delivery Clinical Trials Database (jpharmscidatabase.org). There are 44,789, 18,456, and 12,897 clinical trials registered to evaluate (1) drug delivery technology, (2) biomolecule platform, and (3) drug metabolism and pharmacokinetic-pharmacodynamic interactions; representing 19%-60% increase over the last 3 years.
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PMID:Midyear Commentary on Trends in Drug Delivery and Clinical Translational Medicine: Growth in Biosimilar (Complex Injectable Drug Formulation) Products Within Evolving Collaborative Regulatory Interagency (FDA, FTC, and DOJ) Practices and Enforcement. 2787 65