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)

Doxazosin, a selective inhibitor of alpha 1-adrenergic receptors, when administered alone or in combination with insulin or glucagon to mature ob/ob mice, consistently lowered levels of triglycerides, cholesterol, glycerol, and lactate and increased levels of beta-hydroxybutyrate and glucose. Doxazosin suppressed the tendency of insulin to elevate triglycerides but had no effect on the hypoglycemic response to insulin. Doxazosin and insulin together (but neither alone) lowered free fatty acids (FFA). Glucagon lowered cholesterol and raised glucose but did not affect triglycerides or beta-hydroxybutyrate. Analysis of variance indicates that a simple additive-effects model cannot explain the interactions between doxazosin and insulin on triglycerides, glucose, and FFA. It is suggested that the alpha 1-adrenergic system may contribute to glycemic control and to ambient hypercholesterolemia, especially in the presence of insulin resistance, as in ob/ob mice, and that the hypolipidemic response to alpha 1-adrenergic inhibition may involve insulin pathways.
J Cardiovasc Pharmacol 1989
PMID:Interactions of doxazosin with insulin or glucagon in the ob/ob mouse. 247 Oct 11

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.
Cardiovasc Drugs Ther 1988 Dec
PMID:Lack of effect of nicardipine and diltiazem on glucose- and arginine-induced insulin release in obese subjects. 315 42

The influence of pulsatile perfusion on carbohydrate and lipid metabolism was examined in 40 patients (20 pulsatile and 20 non-pulsatile) who underwent open-heart surgery. The pulsatile assist device was used for pulsatile cardiopulmonary bypass during aortic cross-clamping only, and samples of the mixed venous blood were taken every 20 minutes. There were no statistically significant differences between pulsatile and non-pulsatile groups with respect to plasma levels of glucose, insulin, glucagon, free fatty acids and ketone bodies. However, an increase in the plasma level of noradrenaline was significantly suppressed in the pulsatile group, and triglyceride levels were significantly higher in the pulsatile than in the non-pulsatile group. These data suggest that pulsatile flow attenuates the catecholamine stress response to cardiopulmonary bypass and has a protective effect on liver function during bypass.
J Cardiovasc Surg (Torino)
PMID:Effects of pulsatile cardiopulmonary bypass on carbohydrate and lipid metabolism. 331 20

Since hypothermia is commonly used to lower local and general metabolism during cardiopulmonary bypass, we attempted to identify its specific effects on glucose-insulin interactions. A group of nondiabetic patients undergoing hypothermic (28 degrees C) cardiopulmonary bypass with ischemic (cold) cardiac arrest was compared to a similar group operated on under normothermic conditions with potassium cardioplegia. In the absence of exogenous dextrose administration, hypothermia blocked insulin secretion for the duration of the operation. It also inhibited insulin secretion in response to an exogenous dextrose load (e.g., the priming fluid of the cardiopulmonary bypass circuit) or a glucagon injection, but this inhibition was lifted by rewarming. Blood glucose levels, which during normothermia were mildly elevated even in the absence of dextrose administration, remained normal during the hypothermic phase of cardiopulmonary bypass. By the end of the rewarming period, however, blood glucose levels had reached the same level as observed under normothermic bypass, a fact suggesting that the cold inhibition of hepatic glucose production had been only temporary. Cold inhibition of hepatic glucose production also explains why glucose clearance after a sudden dextrose load was initially faster at low body temperature than at normal temperature. Glucose-clamp studies indicated that insulin resistance was initiated by anesthesia and surgical trauma, and further accentuated by cardiopulmonary bypass, in association with elevated levels of hormones indicative of surgical stress. Regardless of body temperature changes, the assimilation of glucose by nondiabetic subjects during and immediately after bypass called for the infusion of large doses of insulin. A comparison with diabetic subjects showed that insulin-dependent patients (type I diabetes) required no more insulin during cardiopulmonary bypass than normal subjects, whereas patients with type II diabetes exhibited a marked insulin resistance during the operation and in the immediate postoperative period.
J Thorac Cardiovasc Surg 1986 Mar
PMID:Glucose-insulin interactions during cardiopulmonary bypass. Hypothermia versus normothermia. 351 20

Anesthesia, surgical trauma, heparinization, priming volume composition, and temperature control of the heart-lung machine individually affect carbohydrate, protein, or lipid metabolism during cardiac operations. The impact of some of these factors on glucose and insulin regulation was assessed before, during, and after normothermic cardiopulmonary bypass in nondiabetic patients with use of a servo-controlled insulin delivery system. With a glucose-free prime, cardiopulmonary bypass induced a slight hyperglycemia but no endogenous insulin response, suggesting a partial inhibition of insulin secretion. Nonetheless, insulin release could be stimulated by exogenous glucagon. A glucose load in the priming fluid led to marked and persistent hyperglycemia without commensurate insulin release. Elevated stress hormone levels, a concomitant reduction of insulin release and insulin action, and a depression of peripheral glucose utilization, as demonstrated by glucose clamp experiments, contributed to these perturbations of glucose and insulin metabolism. Although the metabolic alterations observed are not critical in routine cardiac operations, they may become clinically significant in postoperative states with unusual persistence of stress conditions.
J Thorac Cardiovasc Surg 1985 Jan
PMID:Alterations of insulin and glucose metabolism during cardiopulmonary bypass under normothermia. 388 Aug 48

The crystalloid solutions used to prime cardiopulmonary bypass pumps frequently contain metabolically active substrates. However, there is a lack of controlled studies to investigate the metabolic response to cardiac operations using different pump primes. We have carried out a prospective, randomized study of 24 patients divided into four groups, each group receiving a different crystalloid prime. The primes contained glucose, lactate, glucose and lactate, or neither glucose nor lactate. Using identical anesthetic, surgical, and perfusion techniques, we estimated the metabolic response to cardiac operation in all patients by frequent blood sampling for measurement of hormone (insulin, glucagon, cortisol, and growth hormone) and metabolite concentrations (glucose, lactate, pyruvate, glycerol, alanine, and 3-hydroxybutyrate) from the day before operation to the seventh postoperative day. The results demonstrated that, after 4 hours postoperatively, the endocrine and metabolic response to cardiac operation was unaffected by the nature of the priming fluid. However, major endocrine and metabolic changes occurred before that time, which were related directly to the glucose and lactate contents of the prime. Very high concentrations of both glucose and lactate were observed at the end of bypass if they were induced in the prime. Given the known dangers of hyperglycemia in cerebral ischemia and the potential gluconeogenic effects of infused lactate, we suggest that glucose-free and lactate-free primes be employed in the extracorporeal circuit.
J Thorac Cardiovasc Surg 1985 Jul
PMID:The effects of four different crystalloid bypass pump-priming fluids upon the metabolic response to cardiac operation. 389 72

The effect of antihypertensive therapy with guanabenz or hydrochlorothiazide (HCTZ) on the secretion of growth hormone, prolactin, insulin, and glucagon was evaluated in double-blind fashion in 45 patients. Fifteen patients were treated with HCTZ, 50 mg twice daily, and 30 patients were treated with twice-daily dosages of guanabenz ranging from 4 to 32 mg. Blood samples for hormone analysis were collected during maintenance therapy when blood pressure was controlled as well as 1 week after the withdrawal of the antihypertensive medications. Serum levels of growth hormone and prolactin were within the normal ranges and were unchanged during treatment with HCTZ or guanabenz at any dose level. Interpatient variability in insulin levels was high, although within-subject insulin levels generally were consistent. No treatment effects were seen for insulin levels among guanabenz- or HCTZ-treated patients. Glucagon levels generally were above the expected range for fasting patients and were lower in patients receiving 4 or 8 mg of guanabenz twice daily than in those receiving 16 mg twice daily (p less than 0.05) and in those treated with HCTZ (p less than 0.01). However, analysis of paired data revealed no changes in glucagon levels upon withdrawal of guanabenz, whereas glucagon levels were higher during HCTZ treatment than after drug withdrawal (p = 0.012). Since guanabenz treatment did not affect the secretion of pancreatic or pituitary hormones, it may be preferable to other centrally acting agents and thiazide diuretics for hypertensive patients who are elderly, overweight, or diabetic.
J Cardiovasc Pharmacol 1984
PMID:Endocrinologic effects of antihypertensive therapy with guanabenz or hydrochlorothiazide. 608 24

Adrenergic receptor response coupling pathways have been shown to differ in hypertrophied hearts in different models of hypertension. To mimic this, chronic subcutaneous infusions of epinephrine (80 nmol/h for up to 13 days) and angiotensin II (AII) (4.3 nmol/h for up to 4 weeks) were given. Myocardial-, basal-, and isoproterenol-, glucagon-, forskolin-, and Gpp(NH)p-stimulated adenylate cyclase were measured. No changes in enzyme activity were seen following AII infusion, even though myocardial hypertrophy was significant. After epinephrine infusion for 6 days, there was a decrease in isoproterenol stimulated enzyme. After 13 days of infusion, cyclase activity, both basal and stimulated, was reduced. We conclude that in hearts from different models of experimental hypertension associated with cardiac hypertrophy, there are different biochemical alterations in the beta-adrenergic receptor response coupling mechanism.
J Cardiovasc Pharmacol
PMID:Adenylate cyclase activity in rat myocardium following chronic infusions of angiotensin II and epinephrine. 620 77

An investigation is presented of the effects of the acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA; 20 mg/kg i.v.) on cardiodynamics and myocardial metabolism in normoxic, anesthetized dogs. POCA induced an initial increase in pulmonary vascular resistance; pulmonary vascular pressure was increased up to 4 h. All other hemodynamic parameters were unchanged. POCA induced a continuous rise in arterial free fatty acid (FFA) level and a marked initial increase in arterial lactate level. Arterial glucose level decreased. Myocardial FFA uptake was almost completely inhibited by POCA; myocardial lactate uptake increased markedly and myocardial glucose uptake remained unchanged. These changes were accompanied by an increase in respiratory quotient from 0.72 to 1.0 and a decrease in myocardial oxygen consumption by 15-20%. In conscious dogs, POCA (20 mg/kg i.v.) induced similar changes in arterial substrate levels. The increase in arterial FFA level was accompanied by an increase in arterial glucagon. Ketone body levels decreased initially but increased simultaneously with glucagon levels. These findings confirm the efficacy of POCA in inhibiting FFA oxidation and, consequently, in decreasing myocardial oxygen consumption. However, possible deleterious effects of the increase in arterial FFA levels on the ischemic myocardium require further experimental evaluation.
J Cardiovasc Pharmacol
PMID:Effects of acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on cardiodynamics and myocardial metabolism in dogs. 620 98

Four patients with metastatic glucagonoma are described. Angiography demonstrated a small avascular primary tumor of the tail of the pancreas in one patient and large hypervascular tumors of the pancreatic head in the other three. Liver metastases, were hypervascular in all four. Including our 4 with 21 cases from the literature, glucagonomas show a 92% incidence of increased tumor vascularity--thus increasing the likelihood of successful angiographic diagnosis. The awareness of clinically subtle or atypical glucagonomas and use of plasma glucagon determination are important factors leading to early diagnosis of these neoplasms. Since angiography can localize the tumor, assess its extent, and detect hepatic metastases, it is essential to the detailed evaluation of glucagonomas.
Cardiovasc Intervent Radiol 1982
PMID:Glucagonoma and its angiographic diagnosis. 630 75


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