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)

Specific binding sites have been demonstrated to exist in the heart for several drugs and hormones such as beta-blocking agents, cardiac glycosides, catecholamines, insulin, glucagon and acetylcholine. The specific binding sites for cardiac glycosides in the human heart have certain properties which make it likely that they are the pharmacological receptors for the therapeutic and toxic actions of digitalis glycosides: they are located in the cell membrane and bind cardioactive steroids reversibly with high affinity: half-maximal receptor binding occurs at approximately 2 nM (approximately 1.5 ng/ml) for digoxin; potassium decreases receptor affinity, calcium increases it; specific binding of ouabain, digoxin or digitoxin is related to inhibition of (Na+ + K+)-ATPase activity--which is supposed to be the receptor enzyme for cardiac glycosides. Human left ventricle contains approximately 1.5 x 10(14) binding sites/g wet weight, right ventricle approximately 0.9 x 10(14). In disease the number of receptors may decrease (hypothyroid states, myocardial infarction) or increase (hyperthyroidism, chronic hypokalaemia). Certain drugs (such as phenytoin) or different temperatures or pH changes cause a change in digitalis-receptor affinity. Thus, the number of receptors and possibly their properties are subject to regulation in clinically relevant situations. Further investigations will probably reveal those pathophysiological states, which allow the explanation of toxicity or digitalis refractoriness.
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PMID:The cardiac glycoside-receptor system in the human heart. 630 38

Diabetic ketoacidosis (DKA) is the commonest endocrine emergency encountered in clinical practice. Although in the last 3 decades the average worldwide immediate mortality has decreased from 10% to 5%, survival has not improved strikingly. The pathogenesis of DKA is currently attributed to a combination of two hormonal abnormalities--a relative insulin insufficiency and stress hormone excess (glucagon, catecholamines, cortisol and growth hormone). Withdrawal of exogenous insulin, pancreatic beta cell failure and insulin resistance are factors leading to relative insulin insufficiency. Factors leading to stress hormone excess include fasting, stress and dehydration. The combination of these two hormonal abnormalities leads to impaired carbohydrate utilization and ketonaemia which in turn results in metabolic acidosis with loss of water through acidotic breaths, rise in plasma lipids, hyperglycaemia and glycosuria leading to osmotic diuresis and further loss of water, excretion of partly neutralised ketoacids via the kidney with loss of cations (Na+ and K+). A net increase in protein catabolism which leads to an increased amino acid flux from muscle and an enhanced load of gluconeogenic precursor to the liver and a rise in blood pyruvate and lactate concentration. The prevention of either of these hormonal abnormalities will prevent the development of DKA. The successful outcome in the treatment of DKA is clearly related to the prompt recognition of the diagnosis and the precipitation factors, the severity of the initial metabolic derangements, the judicious use of fluid and electrolyte replacement, the choice, route and dosage of the insulin therapy and above all the close monitoring and meticulous clinical care of the patient throughout the entire course of the treatment. Current acceptable treatment of DKA include the following: adequate fluid replacement: low dose insulin therapy at frequent intervals; adequate potassium replacement from time of first insulin therapy with ECG monitoring; bicarbonate replacement if pH less than 7.1; broad spectrum antibiotics if infections is suspected and other supportive measures. The role of phosphate and magnesium replacement is still controversial. An awareness of the complications during the treatment of DKA including cerebral edema (paradoxical acidosis), altered central nervous system oxygenation, vascular thrombosis, shock, myocardial infarction, pancreatitis, infection, inhalation of vomitus , overhydration, underhydration , hypoglycaemia, hyperkalemia and hypokalemia all certainly help improve the morbidity and mortality of DKA.
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PMID:Current concepts of the pathogenesis and management of diabetic ketoacidosis (DKA). 633 Dec 71

Glucose-insulin-potassium (GIK) solution is widely used as a cardioplegic infusate for myocardial protection during aortic cross-clamping, to obtain rapid diastolic arrest and preservation of energy stores. Nine male patients with aorto-coronary bypass grafting procedure were studied with regard to the metabolic influence of GIK cardioplegia. Hyperglycemia was induced by the infusion of GIK solution for one week after surgery. The serum level of non-esterified fatty acid was high for one week while the triglyceride level was maintained at a high level only in the early post-operative period. Insulin, glucagon and growth hormone which influence carbohydrate and lipid metabolism were also elevated for one week after infusion of GIK solution. We conclude that the derangement of carbohydrate and lipid metabolism which is provoked by the use of GIK cardioplegia normalizes within two weeks after operation.
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PMID:Metabolic effect of glucose, insulin and potassium cardioplegia. 635 91

The hypothesis has been examined that adenosine is involved in the diuretic and free fatty acid (FFA) - releasing action of xanthines. The effects of theophylline (T), a potent adenosine antagonist, were compared with those of enprofylline (3-propyl xanthine, E), which exerts negligible antagonism of adenosine. Eight healthy male volunteers were given E 1.5 mg/kg, T 5.0 mg/kg or placebo 0.9% saline (P) intravenously in a double-blind, randomized, cross-over investigation. Blood samples were analyzed for E, T, catecholamines (CA: adrenaline, noradrenaline and dopamine), FFA, renin, glucose, glucagon and insulin, and urine was collected at 2-h intervals. T (plasma concentration 53 +/- 8 mumol/l) but not E (11 +/- 2 mumol/l) caused an increase in FFA from 0.42 to 0.86 mmol/l after 90 min. Without affecting the urinary excretion of potassium, T doubled natriuresis and the urine volume as compared to E and P. Neither T nor E had any effect on plasma CA, or on any other of the metabolic parameters studied. E, but not T, produced a small but statistically significant decrease in diastolic blood pressure (5 mmHg) and an increase in heart rate (3 beats/min). It is suggested that the difference between E and T in terms of stimulation of FFA-release and natriuresis may be related to their different ability to antagonize adenosine.
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PMID:Increase in plasma free fatty acids and natriuresis by xanthines may reflect adenosine antagonism. 637 Jul 3

Human and porcine insulin were administered intravenously to a group of healthy volunteers in two different doses (0.075 IU/kg body weight and 0.12 IU/kg body weight) and to two groups of randomly selected patients with pituitary disorders in a dose adapted to their individual glucose tolerance (0.12-0.17 IU/kg body weight for porcine and 0.15-0.18 IU/kg body weight for human insulin). The blood glucose and potassium lowering effect, the feedback regulation of endogenous insulin release, and the liberation of the counterregulatory hormones glucagon, cortisol, adrenocorticotropic hormone (ACTH), prolactin (hPRL), human growth hormone (hGH), and catecholamines were measured before and after injection of human or porcine insulin. The maximal effect, the area under the concentration-time curve, the percentage effect, and the increase above baseline for the two doses of insulin and the two types of insulin were compared. There were no significant differences in the calculated parameters between the two insulin types at the same doses except with prolactin. At 0.075 IU/kg human insulin induced significantly less prolactin release than porcine insulin. Comparing the two doses of the same insulin serum insulin levels, blood glucose, glucagon, norepinephrine, and prolactin were lower at the low dose of each insulin. In addition ACTH and epinephrine were also lower after human insulin at 0.075 IU/kg. The subjective signs of hypoglycemia were less pronounced after human insulin. It is concluded that the biological effects of human insulin are comparable to porcine insulin although prolactin release is significantly reduced after human insulin. If this difference is an indication of different receptor sensitivities for human and porcine insulin in the central nervous system and if the diminished signs of hypoglycemia are a consequence of this, then further studies are required.
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PMID:Counterregulatory hormone release after human and porcine insulin in healthy subjects and patients with pituitary disorders. 638 71

Historically, the sodium ion has been given prominence in relation to cardiovascular disease, perhaps to the exclusion of other ions. Recently, other ions, including chloride, potassium, magnesium and calcium have received increasing attention in relation to hypertension, cardiac arrhythmias, and metabolic derangements. Endocrine factors controlling these ions have also received increasing attention; they include classic hormonal actions as well as neurotransmission and paracrine hormonal actions. Studies indicate that control of the renin-angiotensin-aldosterone system resides in cytosolic calcium ion levels in the juxtaglomerular cell, as well as chloride ion and prostaglandins at the macula densa. Renin release is stimulated by hyperpolarisation of the juxtaglomerular cell induced by beta 1-agonists, parathyroid hormone, glucagon, magnesium and low cytosol calcium. Renin release is inhibited by high calcium, potassium and angiotensin II. Subsequent to renin release, hormonal regulation includes stimulation of converting enzyme activity by cortisol and prostaglandin (PGE2). Other hormonal control includes antidiuretic hormone producing dilution of extracellular electrolytes and augmented peripheral resistance. A recently identified natriuretic factor isolated from cardiac atria appears to be a potent diuretic with actions similar to that of frusemide (furosemide). Other electrolytes have received closer scrutiny. Chloride may play a dominant role in renal sodium reabsorption, responding to prostaglandin levels. Calcium has been recognised as a basic regulator of the secretion of such hormones as noradrenaline, renin, and aldosterone. As well, calcium ion changes are the means by which smooth muscle contraction is effected. Parathyroid hormone and vitamin D regulate the level of this ion in the body. In addition, a high dietary calcium intake appears to play a protective role against hypertension, while calcium channel blockers appear to reduce blood pressure. Endocrine systems play a major role in the protection against acute elevations in serum potassium by means of insulin action and adrenergic modulation of extrarenal potassium disposal. Aldosterone is recognised as the delayed regulator of potassium excretion. Magnesium levels fall in hyperaldosteronism, hyperparathyroidism, and diabetic keto-acidosis, as well as in malnutrition states. A coexisting potassium deficiency may be refractory to therapy until hypomagnesaemia is corrected. The integrated action of these hormones and electrolytes are thus of major importance in regulation of the cardiovascular system.
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PMID:Endocrine physiology of electrolyte metabolism. 638 78

To investigate the role of hormones as mediators of the metabolic response to injury, nine normal male volunteers received a continuous 74-hour infusion of the three 'stress' hormones: cortisol, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Diets were constant and matched on both occasions. Hormonal infusion achieved hormone concentrations similar to those seen following mild-moderate injury. With this alteration in the endocrine environment significant hypermetabolism, negative nitrogen and potassium balances, glucose intolerance, hyperinsulinemia, insulin resistance, sodium retention, and peripheral leukocytosis were observed. Additional studies with single hormone infusions indicated that these responses resulted from both additive and synergistic interactions of the hormones. Triple hormone infusion simulated many of the metabolic responses observed following mild-moderate injury and other catabolic illnesses.
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PMID:Combined hormonal infusion simulates the metabolic response to injury. 643 17

Forty-one endocrine and biochemical serum parameters were studied over a 24-hour span with 6 samples at 4-hour intervals in 20 non-insulin dependent (Type II) diabetics and in 20 non-diabetic subjects matched for sex, age, height and weight. Circadian rhythms were verified by cosinor analysis. Group-synchronized circadian rhythms were detected in diabetic and non-diabetic subjects with no statistically significant difference in any of the rhythm parameters (rhythm adjusted mean, amplitude and acrophase) in: Aldosterone, cortisol, insulin, 17-OH progesterone, prolactin, testosterone, TSH, and in serum albumin, creatine phosphokinase (CPK), serum iron, inorganic phosphate and total protein. Statistically significant (p less than .05) circadian rhythms in both groups with a difference in some parameters between the diabetic and the non-diabetic subjects, which were verified by the Bingham Test (p less than .05) were found with a difference in the mesor in cholesterol, glucose, urea nitrogen (BUN), in the amplitude in C-peptide and in the acrophase in triglycerides, globulin and reverse T3 (rT3). Statistically significant circadian rhythms were detected as a group phenomenon for the diabetics only in progesterone, free and total T4, chloride, calcium, bilirubin and LDH and in the non-diabetic subjects only in ACTH, LH, total T3, alkaline phosphatase, uric acid and potassium. In the remainder of the functions studied, a circadian rhythm was detectable with statistical significance by cosinor analysis as a group phenomenon neither in the diabetics nor in the matched non-diabetic controls (DHEA-S, estradiol, FSH, GH, glucagon, free T3, sodium, GOT and gamma GT). In the absence of a detectable circadian rhythm as group phenomenon, the circadian mean was different between the diabetics and the non-diabetic subjects in sodium, chloride and calcium which were higher in the diabetic patients and serum LDH which was lower. In a comparison of endocrine determinations in the two groups, the circadian mean or mesor in T3 was lower in the diabetics and ACTH higher, without corresponding changes in TSH or in corticosteroids. The circadian time structure of Type II diabetic patients thus seems to be very similar to that seen in non-diabetic subjects of the same sex, age, weight and height. The minor differences found in some rhythm parameters will have to be confirmed or excluded in larger numbers of subjects. The higher circadian mean ACTH concentrations without change in steroid rhythm parameters observed in this group is interesting but will also require confirmation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Circadian time structure of endocrine and biochemical parameters in adult onset (type II) diabetic patients. 652 19

Renal responses to intravenous DL-alanine (ala) and glucagon (GLN) infusions were compared in conscious dogs. Doses of GLN (0.1 microgram/min) that did not increase plasma glucose (PG) concentrations, a physiological effect of GLN, stimulated glomerular filtration rate (G.F.R.). Higher GLN infusion rates (1.0 and 10.0 micrograms/min) stimulated G.F.R., renal plasma flow (R.P.F.), PG, and potassium and urea clearances. Ala infusions (1.3 mmol/min) had similar effects if the dogs had been pre-conditioned by feeding of corn starch, but not if they had been fed a normal diet. This level of ala infusion increased plasma alpha amino nitrogen to levels equivalent to plasma ala levels reported to stimulate GLN secretion. The reason for the lack of responsiveness to ala infusion when the normal diet was fed was not clear. When somatostatin (3.8 micrograms/min), an inhibitor of GLN secretion, and ala were infused simultaneously, G.F.R. was lower than when ala alone was infused. The data suggested that the ala-induced renal effects were mediated by GLN.
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PMID:Glucagon and alanine-induced increases of the canine renal glomerular filtration rate. 661 30

The present study was conducted in 12 healthy volunteers to determine the effect of porcine insulin (0.15 U/kg i.v.) on a number of different metabolic and hormonal parameters measured simultaneously. The nadir of blood glucose (19.0 +/- 2.7 ng/100 ml) is detected 30 min following insulin application, paralleled by suppressed levels of FFA and beta-hydroxybutyrate. The lowest level of potassium (3.39 +/- 0.09 mval/l) is observed 45 min following insulin application. The hormones of counterregulation show an uniform pattern of response. Peak levels of norepinephrine (228.9 +/- 36.0 ng/l) and epinephrine (720.6 +/- 125.6 ng/l) are observed at 30 and 45 min, those of cAMP (33.4 +/- 2.5 pmol/ml), glucagon (0.209 +/- 0.024 ng/ml), ACTH (166.0 +/- 40.1 ng/ml), and prolactin (28.1 +/- 7.8 ng/ml) at 45 min and finally those of cortisol (26.1 +/- 3.3 micrograms/100 ml) and growth hormone (21.6 +/- 3.1 ng/ml) at 60 min following insulin injection. As the blood glucose level is already rising after 30 min it is concluded that the catecholamines and glucagon play a major part in the restitution of normal blood glucose levels. At the end of the test, blood glucose and hormone levels have almost normalized, but FFA and beta-hydroxybutyrate levels are doubled and almost triplicated as compared to the starting point levels.
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PMID:Hormonal and metabolic parameters following insulin-induced hypoglycemia. 675 13


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