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 effects of pulsatile and nonpulsatile flow pattern on pancreas and liver blood flow were studied in nine dogs on cardiopulmonary bypass (CPB). Furthermore, plasma levels of glucose, insulin, glucagon, growth hormone, and cholinesterase were compared in 20 patients subjected to open heart surgery with either pulsatile or nonpulsatile perfusion. Impairment of liver and pancreas function was significantly greater at the end of CPB and 48 h afterwards with nonpulsatile flow as compared with the pulsatile flow pattern. A decrease of intestinal blood flow that was demonstrated in dogs subjected to nonpulsatile perfusion could at least in part be responsible for the difference in postoperative organ function observed in patients after CPB.
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PMID:[Comparative studies on pulsatile and continuous flow during extracorporeal circulation. Effects on liver function and endocrine pancreas secretion]. 45 49

The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output.
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PMID:Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats. 287 43

In 20 patients who underwent open-heart surgery, the plasma concentrations of glucose, insulin, glucagon, growth hormone, free hemoglobin, and cholinesterase were measured before, during and after pulsatile and continuous perfusion. Pulsatile flow was achieved by modification of a roller pump to effect rapid acceleration and slowing. The driving motor was interfaced with a control module to enable ECG-triggered perfusion. In addition to the clinical studies, investigations were performed in 9 dogs to assess the effects of pulsatile and continuous perfusion on liver and pancreas flow during total bypass. During pulsatile perfusion there was a significant increase in insulin which, however, was clearly diminished in relation to glucose levels. The response of the beta-cells was markedly more compromised after continuous than pulsatile perfusion. The secondary postoperative increase in insulin can be accounted for by intravenous administration of glucose and, particularly, after pulsatile perfusion, indicates an almost completely normal response of pancreatic beta-cells. As opposed to the effects of continuous perfusion, the low glucose, glucagon, and growth hormone levels, the insulin increase during and after pulsatile perfusion as well as normal cholinesterase values observed in association with pulsatile perfusion appear to be the result of improved pancreatic and hepatic function. This contention is supported by the experimental finding of significantly increased pancreas and liver perfusion during pulsatile perfusion.
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PMID:[Clinical and experimental studies on pulsatile and continuous flow during extracorporeal circulation (author's transl)]. 700 92

Injury and stress are accompanied by a characteristic hormonal response and altered energy utilisation. Hyperglycaemia and negative nitrogen (N) balance are the leading symptoms of the metabolic changes in the post-operative state. In a prospective, randomised study the efficacy and metabolic effects of glucose-xylitol (GX) 35% (1:1) versus glucose (G) 40% were investigated in patients undergoing major surgery. METHOD. Twenty-four patients undergoing abdomino-thoracic oesophageal cancer surgery were treated in a standardised manner. Total parenteral nutrition was administered over 6 days (kg body wt.-1/day): day of surgery 1-1.25 g carbohydrate (CH); 1st postoperative day (POD) 1.5 g CH, 1 g amino acids (AA); 2nd POD 3 g CH, 1.5 g AA, 1.0 g fat; from 3rd POD 3 g CH, 1.5 g AA, 1.5 g fat (CH GX35% (n = 12) or G40% (n = 12), AA Intrafusin 15%, fat Intralipid 20%). Daily and cumulative N balances, blood-G profiles, blood chemistry, and physical parameters were determined. Glucagon and insulin profiles, CH losses, and oxalic acid secretion were measured. RESULTS. Both groups were comparable for age, body mass index, clinical and physical parameters, and blood chemistry. Mean cumulative N balances after 6 days were -12.0 +/- 16.3 g N for GX35% and -5.6 +/- 19.4 g N for G40% (n.s.; Wilcoxon, P < 0.05). Blood G was similar for both groups with values ranging from 130 to 240 mg/dl on the day of surgery and below 150 mg/dl on the consecutive days. In each group 1 patient needed additional insulin therapy. Glucagon and insulin levels did not show a significant difference between the groups. CONCLUSION. No difference in tolerance and efficacy of nutritional support by GX versus G at a dose of 3 g.kg body wt.-1.d in oesophagectomised patients could be observed. Similar blood G profiles were in accordance with comparable glucagon and insulin levels. Because of the high standard deviations of N balances, differences in efficacy could not be proven. A significantly lower level of pseudocholinesterase (PCHE) for G40% on day 7 might indicate enhanced hepatic protein synthesis in the GX group.
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PMID:[Glucose-xylitol 35% (1:1) versus glucose 40%. Effectiveness and metabolic effects after major surgery]. 797 78

Chronic liver disease is often accompanied by hypoxaemia. We investigated the clinical factors that were related to the arterial oxygen tension (PaO2) in 40 women, all non-smokers with chronic liver disease. They were positive for hepatitis C virus (HCV) antibody and had no evidence of cardiopulmonary disease. Arterial blood was collected from patients at rest (> 15 min) for analysis of blood gases. We determined the correlation between blood gas tension and the clinical variables, i.e. the presence or absence of skin manifestations such as cutaneous spider nevi and palmar erythema, the presence or absence of splenomegaly, vital capacity, forced expiratory volume in one second, V25/body height, serum alanine aminotransferase (AST), serum asparate aminotransferase (ALT), serum cholinesterase, serum gamma-globulin/total protein, excretion of indocyanine green at 15 min (15-min retention rate, ICG level), blood level of ammonia, blood level of endotoxin, plasma level of glucagon and the serum level of type IV collagen-7S. The mean level of PaO2 was 78 +/- 11 (range: 43-95) torr. The mean alveolar-arterial oxygen tension gradient (A-aDO2) was 19 +/- 13 (range: 2-60) torr. Multiple regression analysis used PaO2 and A-aDO2 as objective variables, and the clinical findings as explanatory variables. The explanatory variables that were significantly correlated with blood gas values were ICG level, blood level of endotoxin and presence of skin manifestations. The ICG level showed a high correlation with blood gas values; the ICG level increased, the PaO2 decreased (r = -0.69), while the A-aDO2 showed a high positive correlation (r = +0.78, P < 0.001). Findings suggest that a reduction in hepatic blood flow and hepatocellular function interfere with the inactivation of vasoactive substances such as endotoxin by the liver, leading to the development of skin manifestations, the dilatation of intrapulmonary capillaries and the induction of hypoxaemia.
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PMID:Clinical factors that affect blood gases in non-smoking women with chronic liver disease. 951 26

The fetal and neonatal neurotoxicity of chlorpyrifos (CPF) and related insecticides is a major concern. Developmental effects of CPF involve mechanisms over and above cholinesterase inhibition, notably events in cell signaling that are shared by nonneural targets. In the present study, we evaluated the immediate and long-term effects of CPF exposure of rats during different developmental windows [gestational days (GD) 9-12 or 17-20, postnatal days (PN) 1-4 or 11-14] on the adenylyl cyclase (AC) signaling cascade in the heart and liver. In addition to basal AC activity, we assessed the responses to direct AC stimulants (forskolin, Mn2+); to isoproterenol and glucagon, which activate signaling through specific membrane receptors; and to sodium fluoride, which activates the G-proteins that couple the receptors to AC. Few immediate effects on AC were apparent when CPF doses remained below the threshold for systemic toxicity. Nevertheless, CPF exposures on GD9-12, GD17-20, or PN1-4 elicited sex-selective effects that emerged by adulthood (PN60), whereas later exposure (PN11-14) elicited smaller, nonsignificant effects, indicative of closure of the window of vulnerability. Most of the effects were heterologous, involving signaling elements downstream from the receptors, and thus were shared by multiple inputs; superimposed on this basic pattern, there were also selective alterations in receptor-mediated responses. These results suggest that the developmental toxicity of CPF extends beyond the nervous system, to include cell signaling cascades that are vital to cardiac and hepatic homeostasis. Future work needs to address the potential implications of these effects for cardiovascular and metabolic disorders that may emerge long after the end of CPF exposure.
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PMID:Developmental effects of chlorpyrifos extend beyond neurotoxicity: critical periods for immediate and delayed-onset effects on cardiac and hepatic cell signaling. 1475 71

Organophosphates are developmental neurotoxicants but recent evidence points to additional adverse effects on metabolism and cardiovascular function. One common mechanism is disrupted cell signaling mediated through cyclic AMP, targeting neurohumoral receptors, G-proteins and adenylyl cyclase (AC) itself. Earlier, we showed that neonatal parathion evokes later upregulation of the hepatic AC pathway in adolescence but that the effect wanes by young adulthood; nevertheless metabolic changes resembling prediabetes persist. Here, we administered parathion to neonatal rats (postnatal days 1-4, 0.1 or 0.2 mg/kg/day), straddling the threshold for cholinesterase inhibition, but we extended the studies to much later, 5 months of age. In addition, we investigated whether metabolic challenge imposed by consuming a high-fat diet for 7 weeks would exacerbate neonatal parathion's effects. Parathion alone increased the expression or function of G(i), thus reducing AC responses to fluoride. Receptors controlling AC activity were also affected: beta-adrenergic receptors (betaARs) in skeletal muscle were increased, whereas those in the heart were decreased, and the latter also showed an elevation of m(2)-muscarinic acetylcholine receptors, which inhibit AC. The high-fat diet also induced changes in AC signaling, enhancing the hepatic AC response to glucagon while impairing the cardiac response to fluoride or forskolin, and suppressing betaARs and m(2)-muscarinic receptors; the only change in the cerebellum was a decrease in betaARs. Although there were no significant interactions between neonatal parathion exposure and a high-fat diet, their convergent effects on the same signaling cascade indicate that early OP exposure, separately or combination with dietary factors, may contribute to the worldwide increase in the incidence of obesity and diabetes.
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PMID:Neonatal parathion exposure and interactions with a high-fat diet in adulthood: Adenylyl cyclase-mediated cell signaling in heart, liver and cerebellum. 2007 26

Memory impairment induced by streptozotocin in rats is a consequence of changes in CNS that are secondary to chronic hyperglycemia, impaired oxidative stress, cholinergic dysfunction, and changes in glucagon-like peptide (GLP). Treatment with antihyperglycemics, antioxidants, and cholinergic agonists are reported to produce beneficial effect in this model. Berberine, an isoquinoline alkaloid is reported to exhibit anti-diabetic and antioxidant effect, acetylcholinesterase (AChE) inhibitor, and increases GLP release. However, no report is available on influence of berberine on streptozotocin-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameters of oxidative stress and choline esterase (ChE) activity as marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Thirty days after diabetes induction rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased reduced glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100mg/kg, p.o., twice daily, 30 days) improved cognitive performance, lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats. In another set of experiment, berberine (100mg/kg) treatment during training trials also improved learning and memory, lowered hyperglycemia, oxidative stress, and ChE activity. Chronic treatment (30 days) with vitamin C or metformin, and donepezil during training trials also improved diabetes-induced memory impairment and reduced oxidative stress and/or choline esterase activity. In conclusion, the present study demonstrates treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in diabetic rats.
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PMID:Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes. 2126 64

The incidence of Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) with associated serious complications continues to grow rapidly especially in developed countries. Emerging evidence indicates that AD and T2DM share some common risk factors with comparable pathological features including insulin resistance, amyloidogenesis, glucocorticoid imbalance, inflammation, mitochondrial function and oxidative stress. T2DM has been identified as a risk factor for AD. It has even been hypothesized that AD might be "type 3 diabetes". In addition to amyloid precursor protein processing and tau phosphorylation, commonalities between T2DM and AD in molecular mechanisms provide clues to the identification of novel therapeutic targets such as glucagon-like peptide 1, butyrylcholinesterase, and receptor for advanced glycosylation end products. Although several classes of anti-diabetic drugs are available, achieving long-term glycaemic control without side effects is often challenging. This review summarizes recent evidence for the pathological links, common therapeutic targets, currently the U.S. Food and Drug Administration approved and potential future therapies, giving special attention to ongoing clinical trials of antidiabetic drugs in AD patients and common therapeutic strategies in the management of both AD and T2DM.
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PMID:Fighting Alzheimer's disease and type 2 diabetes: pathological links and treatment strategies. 2405 24