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 case of 34-year old female with incidentally diagnosed adrenal tumour is discussed. The patient complained only of mild headaches and heart palpitations and was not previously treated for hypertension. A diagnosis of pheochromocytoma was made. The diagnostic controversies arose because of subclinical course of the disease, slightly elevated biochemical markers of pheochromocytoma (catecholemines urinary excretion) and non-characteristic result of glucagon stimulation test results. The diagnosis was confirmed by histologic examination of tumour tissue. Presented case indicates the need for thorough clinical and hormonal evaluation of patients with incidentaloma (particularly, when adrenal tumour diameter is larger than 3 cm) to avoid serious complication of surgery treatment in case of misdiagnosis.
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PMID:[An oligosymptomatic case of pheochromocytoma]. 1186 92

Calcium channel antagonists are used primarily for the treatment of hypertension and tachyarrhythmias. Overdose of calcium channel antagonists can be lethal. Calcium channel antagonists act at the L-type calcium channels primarily in cardiac and vascular smooth muscle preventing calcium influx into cells with resultant decreases in vascular tone and cardiac inotropy and chronotropy. The L-type calcium channel is a complex structure and is thus affected by a large number of structurally diverse antagonists. In the setting of overdose, patients may experience vasodilatation and bradycardia leading to a shock state. Patients may also be hyperglycaemic and acidotic due to the blockade of L-type calcium channels in the pancreatic islet cells that affect insulin secretion. Aggressive therapy is warranted in the setting of toxicity. Gut decontamination with charcoal, or whole bowel irrigation or multiple-dose charcoal in the setting of extended-release products is indicated. Specific antidotes include calcium salts, glucagon and insulin. Calcium salts may be given in bolus doses or may be employed as a continuous infusion. Care should be exercised to avoid the administration of calcium in the setting of concomitant digoxin toxicity. Insulin administration has been used effectively to increase cardiac inotropy and survival. The likely mechanism involves a shift to carbohydrate metabolism in the setting of decreased availability of carbohydrates due to decreased insulin secretion secondary to blockade of calcium channels in pancreatic islet cells. Glucose should be administered as well to maintain euglycaemia. Supportive care including the use of phosphodiesterase inhibitors, adrenergic agents, cardiac pacing, balloon pump or extracorporeal bypass is frequently indicated if antidotal therapy is not effective. Careful evaluation of asymptomatic patients, including and electrocardiogram and a period of observation, is indicated. Patients ingesting a nonsustained-release product should be observed in a monitored setting for 12 hours, while those who ingest a sustained-release preparation should be observed for no less than 24 hours. Charcoal should be given to the asymptomatic patient with a history of calcium channel antagonist overdose.
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PMID:Management of calcium channel antagonist overdose. 1253 24

Incidence of CVD in diabetic men was reported to be twice as that of non-diabetics and almost three times greater in diabetic women in the Framingham Study. It is postulated that excessive glycation and oxidation, endothelial dysfunction and increased platelet aggregation may be responsible for endothelial proliferation and thickening of plasmatic membrane in small blood vessels ('lipohyalinosis') leading to lacunar infarction. Prothrombotic state may precipitate a stroke, however, platelet aggregability, elevated fibrinopeptide A (FPA) and D-dimer were not significantly related to stroke in diabetic mellitus (DM), whereas suppressed fibrinolytic activity was a common finding. Of many unknown factors in pathogenesis, the deficient insulin secretion, resistance to action of insulin at level of 'insulin receptors', changes in counter regulatory hormones (e.g. glucagon, pancreatic polypetides, growth hormone, catecholamines, etc.) and decrease in the hepatic sensitivity to insulin action in suppressing glucose output have received more attention. Hyperosmolar state can simulate stroke syndromes. Early recognition and treatment of risk factors such as hypertension or better glycemic control, correction of hyperlipidemia or obesity in diabetic population are important. In diabetic subjects already showing recurrent transient cerebral ischemic attacks (TIAs) or minor strokes, the benefit of antiplatelet agents or antithrombotic therapy in prevention of major strokes is well established. Ramipril has been found to be effective in reducing stroke risk by 33% in diabetic patinets in HOPE study.
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PMID:Cerebrovascular disease in type 2 diabetes mellitus. 1257 84

Hypertension often coexists with hyperlipidemia, insulin resistance, and glucose intolerance, a comorbidity known as metabolic syndrome X. Different antihypertensives have mixed effects on these associated abnormalities. We compared three antihypertensives in the spontaneously hypertensive obese rat model of syndrome X. Moxonidine (4 mg/kg), an imidazoline and alpha2-adrenergic agonist, alpha-methyldopa (200 mg/kg), an alpha2-adrenergic agonist, or the vasodilator hydralazine (10 mg/kg) was given orally for 15 d. All three agents lowered blood pressure equally. Moxonidine significantly reduced fasting plasma insulin, glucagon, cholesterol, triglycerides, and free fatty acids (FFA) compared with untreated controls. In contrast, syndrome X markers were not affected by alpha-methyldopa treatment, and hydralazine reduced only glucagon and FFA. Relative to untreated controls, moxonidine improved glucose tolerance as shown by reduced glucose area under the curve (AUC) (13.6 +/- 2.4 versus 42.5 +/- 9.9 g x min/dl). Insulin AUC was increased (7.4 +/- 0.9 versus 3.9 +/- 1.8 microg x min/ml) as was the plasma C-peptide response to the glucose load. In contrast, alpha-methyldopa and hydralazine worsened glucose tolerance (68 +/- 26 and 110 +/- 21 g x min/ml, respectively) and significantly reduced insulin AUC (2.5 +/- 0.8 and -2.3 +/- 1.0 microg x min/ml, respectively) compared with controls. Moxonidine reduced but alpha-methyldopa and hydralazine elevated glucagon levels after the glucose load. Contrary to the "hemodynamic hypothesis" for the metabolic actions of antihypertensives, which predicts roughly equal benefits, only moxonidine had a positive impact on comorbidities. This unique action suggests a role for direct stimulation of imidazoline receptors.
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PMID:Contrasting metabolic effects of antihypertensive agents. 1455 73

Hypertension is commonly accompanied by obesity, hyperlipidemia, and insulin resistance in humans, a cluster of abnormalities known as metabolic syndrome X. With the notable exception of inhibitors of the renin-angiotensin system, which have mildly beneficial effects on insulin resistance, most antihypertensive agents worsen one or more components of metabolic syndrome X. Second-generation centrally acting antihypertensive agents such as rilmenidine and moxonidine have mixed effects on components of metabolic syndrome X, which might reflect in part actions on two different receptors: I(1)-imidazoline and alpha(2)-adrenergic. Using a rat model of metabolic syndrome X, we sought to separate the influence of these two receptors on glucose and lipid metabolism by using selective antagonists. Rilmenidine and moxonidine acutely raised glucose and lowered insulin, thereby further worsening glucose tolerance. These effects were entirely mediated by alpha(2)-adrenergic receptors. Rilmenidine and moxonidine also lowered glucagon, an effect that was mediated solely by I(1)-imidazoline receptors since it was potentiated by alpha(2)-blockade, but eliminated in the presence of I(1)-antagonists. Lowering of triglyceride and cholesterol levels followed the same pattern as glucagon, implicating I(1)-imidazoline receptors in lipid-lowering actions. Chronic treatment with moxonidine reproduced the beneficial effects on glucagon and lipids while the acute hyperglycemic response did not persist. Thus, alpha(2)-adrenergic receptors mediate an acute deterioration of glucose tolerance, whereas in contrast I(1)-imidazoline receptors appear to mediate the persistent long-term improvements in glucose tolerance. The therapeutic action of I(1)-imidazoline agonists may be primarily mediated through reduced glucagon secretion.
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PMID:The role of I(1)-imidazoline receptors and alpha(2)-adrenergic receptors in the modulation of glucose and lipid metabolism in the SHROB model of metabolic syndrome X. 1502 95

Several methods to assess the total antioxidant capacity (TAC) are available. However, the final value of measured TAC in the sample depends on the procedure used in every specific assay. This makes crucial the comparison of different analytical methods. The aim of our study was to evaluate analytical characteristics and laboratory reliability of two different assays: the ferric-reducing ability (FRAP) assay and a new spectrophotometric test (OXY-adsorbent test, Diacron, Italy). Unselected outpatients referred to the Institute of Clinical Physiology were studied (n = 187, 58 females, 129 males, mean age: 65 +/- 13 years). All blood samples were maintained on ice, centrifuged within 15 minutes after blood collection and then stored at -80 degrees C until performance of assay procedures. OXY assay: The lower limit of sensitivity was 6 micromol HClO/ml. The assay was found to be linear up to 440 micromol HClO/ml (r = -0.99, p < 0.001). Absorbance was linear over a wide concentration range with solutions containing uric acid in purified form (0-1000 micromol/l, r = -0.996, p < 0.001), serum (r = -0.99, p < 0.01) or plasma serially diluted (r = -0.99, p < 0.01). Mean value in plasma samples accounted for 366.2 +/- 7.2 micromol HClO/ml. Mean OXY value in females (353.4 +/- 13.2 micromol HClO/ml) was not different from that detected in males (372 +/- 8.6 micromol HClO/ml). A significant difference was observed between subjects without and with hypertension in serum OXY levels (344.8 +/- 9.9 and 383.2 +/- 10 micromol HClO/ml, p < 0.01, respectively). FRAP assay: The lower limit of sensitivity was 15 micromol/l. Linearity was observed up to 1000 micromol/l (r = 0.998, p < 0.001). Absorbance was linear over a wide concentration range with solutions containing uric acid in purified form (0-1000 micromol/l, r = 0.997, p < 0.001), serum (r = 0.99, p < 0.01) or plasma serially diluted (r = 0.99, p < 0.01). FRAP mean value in plasma samples, evaluated in 102 patients, accounted for 514.1 +/- 19.1 micromol/l. Mean FRAP in females (469 +/- 22.5 micromol/l) was not different from that detected in males (535 +/- 25.6 micromol/l). FRAP vs. OXY: A significant direct relationship was observed when comparing FRAP with OXY levels in the whole population (r = 0.22, p < 0.05). Neither of the methods are expensive and they are speedy and simple to perform. Values are reproducible and linearly correlated to the concentration of antioxidants present in the samples. For this reason, these methods may be considered practicable indicators of total antioxidant capacity, for routinely potential use in every laboratory and useful in all the studies concerning the evaluation of oxidative stress.
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PMID:In vivo total antioxidant capacity: comparison of two different analytical methods. 1506 86

The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.
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PMID:[Pharmacological treatment of obesity]. 1538 15

A lot of interest has engendered in glucagon-like peptide-1 (GLP-1) as an emerging new drug in the treatment of type 2 diabetes. GLP-1 exerts several effects that reduce glycemia in type 2 diabetes patients. We recently also demonstrated that GLP-1 ameliorates endothelial dysfunction in type 2 diabetes mellitus patients with established coronary heart disease, suggesting a new important cardioprotective role for GLP-1. Because hypertension is overrepresented in diabetes and is adversely influencing survival, we have now investigated direct GLP-1 effects on vascular beds in a rat organ bath model. It was found that GLP-1 relaxed femoral artery rings in a dose-response manner. The relaxant effect from GLP-1 was completely inhibited by the specific GLP-1 receptor antagonist, exendin(9-39). Neither the specific nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine, nor removing of endothelium, affected the GLP-1 relaxant effect. In conclusion, we now report a direct vascular action of GLP-1, relaxing conduit vessels independently of NO and the endothelium.
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PMID:Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism. 1558 29

Pheochromocytomas (pheo) cause the most dramatic, life-threatening crises in all of endocrinology. A proper screening for pheo must be performed in any patient who has: 1) episodic headaches, tachycardia, and diaphoresis; 2) family history of pheo or multiple endocrine neoplasia; 3) incidental suprarenal mass; 4) paroxysms of tachyarrhythmias or hypertension; 5) adverse cardiovascular responses to anesthetic agents, histamine, phenothiazine, tricyclic antidepressants, etc); and 6) spells occurring during exercise, straining, etc. The key to diagnosing pheo is to suspect it, then to confirm it. Early recognition of its presence is critical to avoiding significant morbidity and mortality. Once suspected, the diagnosis can be confirmed with biochemical testing in virtually all patients. The combination of resting plasma catecholamines > or =2000 pg/mL and urinary metanephrines > or =1.8 mg/24 h has a diagnostic accuracy of 98% in both sporadic and hereditary pheos. When available, measurement of plasma free metanephrines should be performed especially in hereditary pheos. Provocative (glucagon) and suppression tests (clonidine) may be necessary when baseline measurements are inconclusive. CT and MRI are equally sensitive for localization (98% and 100%, respectively), but have lower specificities (70% and 67%). MIBG is 100% specific, but less sensitive (78%). The availability of various medical (selective alpha-1- and beta-adrenergic receptor antagonists, calcium channel blockers) and surgical modalities have made successful management more promising than ever before.
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PMID:Pheochromocytoma: current perspectives in the pathogenesis, diagnosis, and management. 1576 46

The world witnesses an explosive increase in diabetes, demanding intensified prevention and treatment not least for the low-income population. The plant, Stevia rebaudiana Bertoni, has been used for the treatment of diabetes in traditional medicine. We have previously demonstrated that stevioside, a diterpene glycoside isolated from the plant Stevia rebaudiana Bertoni, possesses insulinotropic, glucagonostatic, antihyperglycemic, and blood pressure-lowering effects in animal studies. We have also found that a dietary supplement, Abalon, of soy protein, isoflavones, and cotyledon fiber has beneficial effects on cardiovascular risk markers in type 2 diabetes. The aim of this study was to investigate if the combination of stevioside and a dietary supplement of soy protein possesses beneficial qualities in the treatment of type 2 diabetes and the metabolic syndrome. We randomized male Zucker diabetic fatty rats into 4 groups and fed them the different test diets for 10 weeks: (A) standard carbohydrate-rich laboratory diet (chow), (B) chow+stevioside (0.03 g/kg body weight [BW] per day), (C) 50% soy (Abalon)+50% chow (adjusted for vitamins and minerals), and (D) 50% soy (Abalon)+50% chow+stevioside 0.03 g/kg BW per day. We measured plasma glucose, blood pressure, weight, and food intake once weekly. The animals were equipped with an intra-arterial catheter, and at week 10, the conscious rats underwent an intra-arterial glucose tolerance test (2.0 g/kg BW). Stevioside exerts beneficial effects in type 2 diabetic Zucker diabetic fatty rats, that is, lowers blood glucose (area under the glucose curve [AUC(30min)]: group A vs B, a 19% reduction; and group C vs D, a 12% reduction; P<.001). We did not detect any effect on insulin or glucagon responses. After 2 weeks of treatment, a decrease in the systolic blood pressure was observed in the stevioside-treated groups (P<.01). Abalon had beneficial effects on cardiovascular risk markers, that is, (1) lowers total cholesterol (P<.01), (2) reduces triglycerides (P=.01), and (3) reduces free fatty acids (P<.001). The combination of stevioside and soy supplementation appears to possess the potential as effective treatment of a number of the characteristic features of the metabolic syndrome, that is, hyperglycemia, hypertension, and dyslipidemia. A long-term human study of the concept in type 2 diabetic subjects is needed to verify these promising results in animal diabetes.
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PMID:Preventive effects of a soy-based diet supplemented with stevioside on the development of the metabolic syndrome and type 2 diabetes in Zucker diabetic fatty rats. 1612 30


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