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 hormonal regulation and enzymatic basis of endogenous lipolysis in heart are not yet completely elucidated. The lysosomal fraction from rat heart appeared to be markedly enriched in triglycerides and a significant reduction in triglycerides in this fraction was found after prolonged perfusion or stimulation of lipolysis with glucagon. The enhanced rate of lipolysis, measured as glycerol release from the isolated perfused rat heart, was abolished 10-15 min after continuous glucagon administration. Omission of glucagon for another 60 min restored the ability of glucagon to stimulate lipolysis, indicating the limited availability of endogenous triglycerides and the presence of a transfer-system for triglycerides from a non-metabolically active pool to a metabolically active pool. The enhanced lipolysis induced by low-flow ischemia was found to be inhibited by the lysosomotropic agent methylamine (5 mM). Methylamine-perfusion during low-flow ischemia was accompanied by an increased recovery of myocardial triglycerides in the lysosomal fraction. The possible role of lysosome-like particles in myocardial triglyceride homeostasis was further investigated by studying the kinetics of uptake and degradation of labeled triglycerides by membrane-particles recovered in the subcellular fraction enriched with lysosomal marker enzymes. It appeared that isolated lysosomal membranes take up added triglycerides at an average rate of 30 nmoles/min/g protein. The bulk of these triglycerides taken up is stored whereas 20% is degraded to diglycerides and free fatty acids. More than 90% of the free fatty acids formed were released from the lysosomes into the supernatant. The uptake and degradation of triglyceride-filled liposomes by isolated myocardial lysosomes was inhibited during incubation with methylamine (5 mM). On the other hand, a lowering of pH during in vitro incubation increased the rate of uptake and degradation of added triglycerides by isolated lysosomes. These results indicate that lysosomes or lysosome-like particles are involved in the enhanced lipolysis during myocardial ischemia.
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PMID:Involvement of lysosome-like particles in the metabolism of endogenous myocardial triglycerides during ischemia/reperfusion. Uptake and degradation of triglycerides by lysosomes isolated from rat heart. 235 Mar 29

Glucagon and concanavalin A were administered into cell cultures of mice peritoneal macrophages and human intima aorta simultaneously with atherogenous blood serum, obtained from patients with ischemic heart disease, or with acetylated and native low density lipo-proteins. Their effect was dissimilar: glucagon decreased accumulation of intracellular cholesterol and the rate of 3H-thymidine incorporation into these cells, while concanavalin A increased the patterns studied. Cellular lysosomes appear to participate in atherogenesis, these results suggest that regulation of lysosomal apparatus may occur at the step of secondary lysosomes formation.
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PMID:[The effect of glucagon and concanavalin A on cholesterol accumulation in mouse peritoneal macrophages and human aorta intima cells]. 261 47

In non-obese, non-diabetic patients suffering acute myocardial infarction, angina pectoris, previous myocardial infarction and peripheral vascular disease, the plasma levels of glucose, insulin, C-peptide and glucagon were determined in basal condition and during an intravenous glucose tolerance test. In the four groups there was a high frequency of glucose intolerance. Basal hyperinsulinism was present in all groups; in groups; in those which maintained normal glucose tolerance there was a high B-cell response to the sugar. Basal hyperglucagonemia was found in the early stage of acute ischemic heart disease, in patients with previous myocardial infarction and in those with peripheral vascular disease. The elevated plasma glucagon levels may play a role in the complex disturbance of carbohydrate metabolism present in patients with atherosclerotic vascular disease.
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PMID:Carbohydrate metabolism and plasma levels of insulin and glucagon in patients with atherosclerotic vascular disease. 304 64

The metabolic effects of calcium channels blockers have already been studied both in normal and diabetic humans and results were quite controversial, depending on the drug used, the dose administered, and the type of patient. Little information exists on the use of Ca2+ antagonists in obese people, even if these persons are a population risk group for developing diseases in which these drugs may be requested for treatment. Thus, we evaluated, in obese humans, the metabolic effects of two Ca2+ antagonist drugs recently made commercially available to treat diseases such as hypertension and ischemic heart disease: nicardipine and diltiazem. Sixteen obese subjects were submitted to an intravenous glucose tolerance test (0.33 g/kg) (IVGTT) and an arginine test tolerance (30 g in 30 minutes) (ATT) before and after a week of oral treatment with nicardipine (60 mg/day) or diltiazem (360 mg/day). Plasma values of glucose, insulin, and C-peptide during IVGTT, and of glucose, insulin and glucagon during ATT did not show any modification during treatment with either drug. Thus the Ca2+ antagonists, nicardipine and diltiazem, at therapeutic doses in obese subjects do not significantly affect glucose tolerance or insulin and glucagon release.
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PMID:Lack of effect of nicardipine and diltiazem on glucose- and arginine-induced insulin release in obese subjects. 315 42

The toxic effects associated with rapid lipid mobilization and a high plasma free fatty acid (FFA) concentration produced by glucagon were evaluated. Glucagon (0.5 mg/kg of body wt) was injected intravenously into nonfasting geese. The geese developed rapid respirations and high plasma FFA levels within 15 min after the glucagon injection; three of eleven died. Control geese, injected with saline, did not exhibit toxic signs. Peak FFA concentrations developed 15 min after glucagon and high levels persisted for over 90 min. Geese injected with glucagon frequently developed electrocardiographic abnormalities that included supraventricular tachycardia, premature ventricular contractions, and signs of myocardial ischemia. Light and electron microscopy revealed acute myocardial degeneration and fatty infiltration of the liver. The increase in plasma FFA concentrations and toxic effects were not prevented by pretreatment with nicotinic acid or propranolol.
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PMID:Toxic effects of glucagon-induced acute lipid mobilization in geese. 572 81

To the extent that they have deficient glucagon secretory responses to plasma glucose decrements, as they commonly do, patients with insulin-dependent diabetes mellitus (IDDM) are dependent on epinephrine-mediated beta-adrenergic mechanisms to promote recovery from hypoglycemia. Thus, they are at increased risk for prolonged hypoglycemia if treated with a nonselective beta-adrenergic antagonist such as propranolol. If the hyperglycemic actions of epinephrine are mediated through beta 2-adrenergic mechanisms, therapeutic efficacy (e.g., for hypertension or ischemic heart disease) could be accomplished without increased risk of hypoglycemia by selective beta 1-adrenergic blockade in such patients. However, oral administration of the relatively selective beta 1-adrenergic antagonist metoprolol (100 mg) and of the nonselective beta-adrenergic antagonist propranolol (80 mg) both impaired recovery from insulin-induced hypoglycemia in patients with IDDM. Thus, at a dose of 100 mg, oral metoprolol is not safer than oral propranolol with respect to recovery from hypoglycemia in patients with IDDM.
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PMID:Oral propranolol and metoprolol both impair glucose recovery from insulin-induced hypoglycemia in insulin-dependent diabetes mellitus. 637 17

The potential effects of growth hormone (GH) deficiency in adults and the importance of GH secretion in adult life have only been recognized and documented recently. It has been suggested that GH-deficient adults may have premature mortality, abnormalities in body composition and bone density with impaired physical performance and psychological well-being, which are sometimes improved by GH replacement. It is essential, therefore, to establish reliable standards to define GH deficiency in adults. Patients with possible GH deficiency often have primary pituitary or hypothalamic disorders or have undergone surgery or radiotherapy, and thus show evidence of a failure of one of the other pituitary hormones. Several biochemical approaches have been studied to define GH deficiency in the adult and no universal consensus has yet been reached. The most widely established criterion is the peak serum GH concentration achieved during a provocative test, usually the insulin tolerance test (ITT), or following other pharmacological stimuli (e.g. glucagon, arginine, clonidine or GH-releasing factor) but, alternatively, a more physiological stimulus (such as sleep, fasting or exercise) has been used. Spontaneous circulating levels of hormones of the GH axis [24-hour integrated GH concentration, serum insulin-like growth factor I (IGF-I) or IGF-binding protein-3] have been used in the diagnosis of childhood GH deficiency. They have been tested in adults as well but seem to have a more limited role. There are several factors complicating the evaluation of these results. Basal and stimulated GH and IGF-I levels decline with age and with obesity, levels tend to be higher in females and are dependent on nutritional and physical status. The ITT potentially has some risk attached, e.g. in the presence of ischaemic heart disease, but it has proved to be safe in general when used in specialized departments. Other tests are less reliable; releasing hormone tests only assess the readily releasable stores within the pituitary and not the physiological secretory status. The 'cut-off' point for the definition of subnormal responses ideally needs to be set for each provocative test, for each age group, for each degree of obesity and for both sexes. There is considerable variability in GH assays among different laboratories, which makes it difficult to compare hormone levels. The reproducibility of provocative tests can also be variable. An advantage of the hypoglycaemia and glucagon tests is that they allow simultaneous assessment of the adrenocorticotropic hormone reserve.
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PMID:Diagnosis of growth hormone deficiency in adults. 895 Jun 17

Diabetic ketoacidosis (DKA) is the most common hyperglycemic emergency in patients with diabetes mellitus. DKA most often occurs in patients with type 1 diabetes, but patients with type 2 diabetes are susceptible to DKA under stressful conditions, such as trauma, surgery, or infections. DKA is reported to be responsible for more than 100 000 hospital admissions per year in the US, and accounts for 4-9% of all hospital discharge summaries among patients with diabetes. Treatment of patients with DKA uses significant healthcare resources and accounts for 1 out of every 4 healthcare dollars spent on direct medical care for adult patients with type 1 diabetes in the US. Recent studies using standardized written guidelines for therapy have demonstrated a mortality rate of less than 5%, with higher mortality rates observed in elderly patients and those with concomitant life-threatening illnesses. Worldwide, infection is the most common precipitating cause for DKA, occurring in 30-50% of cases. Urinary tract infection and pneumonia account for the majority of infections. Other precipitating causes are intercurrent illnesses (i.e., surgery, trauma, myocardial ischemia, pancreatitis), psychological stress, and non-compliance with insulin therapy. The triad of uncontrolled hyperglycemia, metabolic acidosis and increased total body ketone concentration characterizes DKA. These metabolic derangements result from the combination of absolute or relative insulin deficiency and increased levels of counter-regulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Successful treatment of DKA requires frequent monitoring of patients, correction of hypovolemia and hyperglycemia, replacement of electrolyte losses, and careful search for the precipitating cause. Since the majority of DKA cases occur in patients with a known history of diabetes, this acute metabolic complication should be largely preventable through early detection, and by the education of patients, healthcare professionals, and the general public. The frequency of hospitalizations for DKA has been reduced following diabetes education programs, improved follow-up care, and access to medical advice. Novel approaches to patient education incorporating a variety of healthcare beliefs and socioeconomic issues are critical to an effective prevention program.
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PMID:Diabetic ketoacidosis: risk factors and management strategies. 1587 46

It has been shown that lipid profiles do not differ between pancreas recipients with systemic and portal venous anastomosis. However, it is unclear whether venous drainage from the transplanted pancreas has an impact on recipient atherogenesis and if other factors should be considered. Increased concentration of proinsulin correlates with tachycardia and other risk factors for ischemic heart disease. The aim of this study was to compare proinsulin levels in different types of pancreatic graft venous drainage. Twenty-four simultaneous pancreas and kidney transplantation (SPK) recipients with systemic venous drainage (group S, n = 12) and portal venous drainage (group P, n = 12) under identical immunosuppressive treatment were prospectively observed during 24 months. Following transplantation, only recipients with normoglycemia, normal HbA1c, and normal serum creatine were evaluated. Proinsulin was assessed in fasting state; after glucagon stimulation (Delta-proinsulin), and during oral 75-g glucose tolerance test twice: between 3 and 6 months and 12 to 24 months posttransplantation. All SPK patients had higher proinsulin concentration in fasting state compared with age-matched healthy controls. After stimulation, proinsulin level did not significantly differ between groups; the type of the pancreas venous anastomosis did not change the release of proinsulin and should not have impact on cardiovascular risk factors.
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PMID:Proinsulinemia in simultaneous pancreas and kidney transplant recipients. 1650 25

Vitamin E has the ability to scavenge a wide spectrum of free radicals, including singlet oxygen, superoxide, and hydroxyl radicals. It has beneficial effects against several other disorders, such as atherosclerosis and ischemic heart disease, because it acts as a transcriptional regulator for gene expression via a transcription factor TAP. The beneficial effect of vitamin E on plasma insulin and glucagon levels was examined using radioimmunoassay technique. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at a dose of 60 mg/kg body weight. Vitamin E was given at a dose of either 0.2 mg, 0.4 mg, or 0.8 mg per animal 10 days before and after the onset of diabetes. Vitamin E significantly (P < 0.05) increased plasma insulin levels in normal rats but failed to increase the plasma insulin level in diabetic rats. In contrast, vitamin E caused a significant (P < 0.05) reduction in plasma glucagon level in rats treated before and after the onset of diabetes. Vitamin E may ameliorate some diabetic complication via reduction in the level of circulating glucagon.
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PMID:Vitamin E decreases the hyperglucagonemia of diabetic rats. 1715 20


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