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)

We have investigated the direct effect of glucagon on collagenase-dispersed adrenocortical cells obtained from consenting patients undergoing unilateral adrenalectomy and nephrectomy for renal cancer. Dispersed cells, actually a mixture of zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells, were incubated with glucagon (from 10(-10) to 10(-6) M) alone or in the presence of 10(-9) M angiotensin-II, 10(-10) M ACTH or 10(-5) M forskolin, and the effects on aldosterone, cortisol and cyclic-AMP (cAMP) production were measured by radioimmune assay. Glucagon concentration-dependently inhibited ACTH-stimulated cortisol production and ACTH- or forskolin-enhanced cAMP release, minimal and maximal effective concentrations being 10(-9) and 10(-7) M. The effects of glucagon were suppressed by 10(-5) M Des-His1-[Glu9]glucagon amide, an antagonist of glucagon receptors (glucagon-A). Reverse transcription-polymerase chain reaction did not reveal the presence of specific glucagon-receptor mRNA in the human adrenal cortex. However, autoradiography demonstrated the presence of [125I]glucagon binding sites in the ZF/R, which were displaced by glucagon but not by ACTH. Taken together, these findings suggest that glucagon, through the activation of unidentified receptors located on ZF/R cells, inhibits adenylate cyclase, thereby dampening glucocorticoid response to ACTH.
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PMID:Glucagon inhibits ACTH-stimulated cortisol secretion from dispersed human adrenocortical cells by activating unidentified receptors negatively coupled with the adenylate cyclase cascade. 1096 31

The distal tubule reabsorbs approximately 10% of the filtered Mg(2+), but this is 70-80% of that delivered from the loop of Henle. Because there is little Mg(2+) reabsorption beyond the distal tubule, this segment plays an important role in determining the final urinary excretion. The distal convoluted segment (DCT) is characterized by a negative luminal voltage and high intercellular resistance so that Mg(2+) reabsorption is transcellular and active. This review discusses recent evidence for selective and sensitive control of Mg(2+) transport in the DCT and emphasizes the importance of this control in normal and abnormal renal Mg(2+) conservation. Normally, Mg(2+) absorption is load dependent in the distal tubule, whether delivery is altered by increasing luminal Mg(2+) concentration or increasing the flow rate into the DCT. With the use of microfluorescent studies with an established mouse distal convoluted tubule (MDCT) cell line, it was shown that Mg(2+) uptake was concentration and voltage dependent. Peptide hormones such as parathyroid hormone, calcitonin, glucagon, and arginine vasopressin enhance Mg(2+) absorption in the distal tubule and stimulate Mg(2+) uptake into MDCT cells. Prostaglandin E(2) and isoproterenol increase Mg(2+) entry into MDCT cells. The current evidence indicates that cAMP-dependent protein kinase A, phospholipase C, and protein kinase C signaling pathways are involved in these responses. Steroid hormones have significant effects on distal Mg(2+) transport. Aldosterone does not alter basal Mg(2+) uptake but potentiates hormone-stimulated Mg(2+) entry in MDCT cells by increasing hormone-mediated cAMP formation. 1,25-Dihydroxyvitamin D(3), on the other hand, stimulates basal Mg(2+) uptake. Elevation of plasma Mg(2+) or Ca(2+) inhibits hormone-stimulated cAMP accumulation and Mg(2+) uptake in MDCT cells through activation of extracellular Ca(2+)/Mg(2+)-sensing mechanisms. Mg(2+) restriction selectively increases Mg(2+) uptake with no effect on Ca(2+) absorption. This intrinsic cellular adaptation provides the sensitive and selective control of distal Mg(2+) transport. The distally acting diuretics amiloride and chlorothiazide stimulate Mg(2+) uptake in MDCT cells acting through changes in membrane voltage. A number of familial and acquired disorders have been described that emphasize the diversity of cellular controls affecting renal Mg(2+) balance. Although it is clear that many influences affect Mg(2+) transport within the DCT, the transport processes have not been identified.
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PMID:Magnesium transport in the renal distal convoluted tubule. 1115 54

The effects of combined general anaesthesia and epidural analgesia in various endocrine and metabolic parameters were studied before, during, at the end, and 72 h after upper abdominal surgery, in an effort to further elucidate the role of epidural analgesia in the endocrine and metabolic response. 50 patients were randomly assigned into groups A and B, which received general anaesthesia alone and combined general anaesthesia and epidural analgesia, respectively. The effects of surgical stress in the plasma concentration of ACTH (P <0.001), cortisol (P <0.01), aldosterone (P <0.05), FFA (P <0.05) and glucose (P <0.01) were significantly less pronounced in the group of patients who received combined general anaesthesia and epidural analgesia. However, there were no significant differences between the two groups in regard with plasma TSH, T3, T4, glucagon or Na+ concentration. These results indicate that the combination of general anaesthesia and epidural analgesia attenuate, but does not inhibit, the endocrine and metabolic response to upper abdominal surgery.
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PMID:Epidural analgesia attenuates the systemic stress response to upper abdominal surgery: a randomized trial. 1158 7

Many lines of evidence have shown that preproglucagon-derived peptides affect steroid secretion from dispersed adrenocortical cells, and that streptozotocin (STZ)-induced experimental diabetes alters adrenocortical-cell function. Hence, we compared the effects of glucagon, glucagon-like peptide (GLP)-1 and GLP-2 on basal and ACTH-stimulated secretion of dispersed adrenocortical cells from normal and STZ-induced diabetic rats. We also examined the effects of exendins (EX) 3 and 4, because EX4 is known to be a potent and long-lasting agonist of GLP-1 receptors. STZ-induced diabetes moderately enhances basal and ACTH-stimulated secretion from dispersed zona glomerulosa (ZG) cells, without significantly affecting corticosterone production from dispersed zona fasciculata-reticularis (ZF/R) cells. In normoglycemic rats, glucagon increased basal aldosterone and corticosterone secretion from ZG and ZF/R cells, GLP-2 raised both basal and ACTH-stimulated aldosterone secretion and ACTH-stimulated corticosterone output, and EX4 increased basal corticosterone secretion. In contrast, glucagon, GLP-2 and EX4 did not elicit secretory responses from adrenocortical cells of diabetic rats. GLP-1 and EX3 did not alter secretion of dispersed adrenocortical cells of either normal or STZ-treated rats. Taken together, our findings indicate that preproglucagon-derived peptides enhance steroid secretion from adrenocortical cells of normal, but not STZ-induced diabetic rats. It is suggested that the prolonged exposure to low concentrations of insulin causes unresponsiveness of adrenocortical cells to glucagon, GLP-2 and EX4, which may contribute to the hyporeninemic hypoaldosteronism and alterations in glucocorticoid metabolism occurring in experimental diabetes.
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PMID:Effects of preproglucagon-derived peptides and exendins on steroid-hormone secretion from dispersed adrenocortical cells of normal and streptozotocin-induced diabetic rats. 1279 20

The hepatorenal syndrome (HRS) is related to vasoconstriction of the renal cortex induced by systemic hypovolemia that follows splanchnic vasodilatation as the primary event in the cascade of hemodynamic changes associated with portal hypertension. We evaluated the effects of octreotide, a splanchnic vasoconstrictor, on HRS in cirrhotic patients. We compared the effects of octreotide infusion (50 microg/h) to placebo using a randomized, double-blind, cross-over design over 2, 4-day periods. Nineteen patients were included, and 14 patients could complete the 2 phases of the study (group 1: placebo first; n = 8 and group 2: octreotide first; n = 6) The end point of the study was to evaluate improvement in renal function as defined by a 20% decrease in serum creatinine value after a 4-day treatment as compared with baseline. In all the patients, a normal central venous pressure was maintained by daily intravenous administration of 2 units of albumin. The 2 groups were similar with regard to demographic data and liver and kidney function parameters at baseline. Improvement in renal function was observed in 2 patients after the placebo and 1 patient after octreotide infusion in group 1 and in 2 patients after octreotide infusion and 1 patient after placebo in group 2 (P = not significant). In addition, treatment with octreotide infusion did not result in significant changes in creatinine clearance, daily urinary sodium, plasma renin activity, plasma aldosterone and glucagon levels, or renal and mesenteric artery resistance indices as measured by Doppler ultrasonography. In conclusion, the present study demonstrates that, under our experimental conditions, octreotide infusion combined with albumin is not effective for the treatment of HRS in cirrhotic patients.
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PMID:Octreotide in hepatorenal syndrome: a randomized, double-blind, placebo-controlled, crossover study. 1283 7

Exendin-4 (Ex4) is a potent and long-lasting agonist of glucagon-like peptide-1 (GLP-1), which has been previously found to stimulate pituitary-adrenal axis in the rat. Aim of the present study was to gain insight into the mechanism(s) involved in the Ex4-induced rise in the rat plasma concentrations of ACTH, aldosterone and corticosterone. Preliminary time- and dose-response studies showed that the maximum stimulating effect of Ex4 occurred within 1 or 2 h and at dose ranging from 0.5 to 2.0 nmol/100 g body weight. The GLP-1 receptor (GLP-1R) antagonist Ex(9-39) did not significantly affect ACTH, aldosterone and cortico-sterone responses to Ex4. Neither the administration of CRH and arginine vasopressin (AVP)-receptor antagonists nor adrenal demedullation prevented pituitary-adrenal axis responses to Ex4. The prolonged (4 or 6 days) suppression of the pituitary ACTH release by dexamethasone impaired corticosterone, but not aldosterone response to Ex4. The following conclusions are drawn: i) Ex4 stimulates rat pituitary-adrenal axis through receptors other than the classic GLP-1R; ii) neither CRH and AVP nor medullary catecholamines are involved in the Ex4-induced stimulation of ACTH release; iii) ACTH stimulation accounts for the rise in corticosterone plasma concentration; and iv) the aldosterone secretagogue effect of Ex4 occurs via a mechanism independent of the stimulation of either ACTH or medullary catecholamines.
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PMID:Exendin-4, a GLP-1 receptor agonist, stimulates pituitary-adrenocortical axis in the rat: Investigations into the mechanism(s) underlying Ex4 effect. 1285 24

The first hours of extracorporeal life support (ECLS) are commonly marked by new hemodynamic instability without a known etiology. We measured hormone and catecholamine concentrations in six ECLS primed circuits immediately before joining the patient's circulation to assess a potential role of these agents in this condition. The following hormones were significantly below the lower end of the normal range for the first week of life (data are presented as mean +/- SEM): cortisol 1.95 +/- 0.15 microg/dl (p < 0.001), aldosterone 3.73 +/- 0.74 ng/dl (p < 0.05), free thyroxine 1.2 +/- 0.1 ng/dl (p < 0.05), free triiodothyronine 0.53 +/- 0.03 pg/ml (p < 0.001), thyroid stimulating hormone 0.31 +/- 0.05 microU/ml (p < 0.001), growth hormone (GH) 0.09 +/- 0.01 ng/ml (p < 0.001), estradiol 38.3 +/- 3.72 pg/ml (p < 0.001), IGF-BP1 0.95 +/- 0.1 ng/ml (p < 0.001), glucagon 26 +/- 1.2 pg/ml (p < 0.001), epinephrine 17.3 +/- 3.7 pg/ml (p < 0.001), and norepinephrine 127 +/- 27 pg/ml (p < 0.05). No dopamine was detected. Normal hormone concentrations included IGF-I, IGF-BP3, insulin, parathyroid hormone, leptin, and testosterone. Critically low concentrations of cortisol, thyroid hormones, GH, IGF-BP1, glucagon and catecholamines were measured in the ECLS circuit even though it was primed with fresh frozen plasma. These concentrations may cause significant and precipitous dilutional reductions in the patient's circulating levels immediately after connection to the ECLS circuit and hence contribute to hemodynamic instability.
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PMID:Critically low hormone and catecholamine concentrations in the primed extracorporeal life support circuit. 1476 93

Classic congenital hyperplasia (CAH) is characterized by impaired adrenocortical function with a decrease in cortisol and aldosterone secretion and an increase in androgen secretion. Adrenomedullary function is also compromised due to developmental defects in the formation of the adrenal medulla, leading to decreased production of epinephrine. To examine the response to a natural stressful stimulus in patients with classic CAH, we studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with CAH and nine healthy controls matched for gender, age, and percent body fat. The same relative workload was applied, based on individual maximal aerobic capacity, and all patients received their usual glucocorticoid and mineralocorticoid replacement. When compared with their normal counterparts, patients with CAH had significantly lower epinephrine levels both at baseline and at peak exercise (P < 0.01), whereas norepinephrine levels did not differ. Blood glucose concentrations were similar at baseline, but the normal exercise-induced rise observed in the healthy controls was significantly blunted in the CAH patients (P < 0.01). Peak heart rate was also lower in CAH patients than healthy controls (P < 0.05). As expected, the normal exercise-induced increase in cortisol was not observed in patients with CAH. No significant differences were found in serum levels of insulin, glucagon, GH, lactate and free fatty acids, blood pressure, or ability to sustain exercise between the two groups. Patients with CAH replaced with glucocorticoids have decreased adrenomedullary reserve and impaired exercise-induced changes in glucose but normal short-term high-intensity exercise performance. Whether the combination of epinephrine and cortisol deficiency poses a risk for hypoglycemia and/or decreased endurance during long-term physical stress has to be determined.
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PMID:Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glucose elevation in response to high-intensity exercise. 1476 67

Leptin is a 147-amino acid adipose tissue-secreted hormone, which acts via several subtypes of receptors, the main and better known variants of which are named Ob-Ra and Ob-Rb. Structure-activity relationship studies pointed out the importance of the N-terminal and C-terminal amino-acid sequences 22-115 and 116-166, respectively, for the biological and receptor binding activities of leptin. Evidence has been provided that leptin affects corticosteroid-hormone and insulin secretion, and therefore we have investigated in the rat the expression of leptin receptor expression in adrenal cortex and pancreatic islets, as well as the effects of the acute treatment with leptin and leptin fragments 150-167, 138-167, 93-105, 22-56 and 26-39 on the plasma concentrations of aldosterone, corticosterone, insulin and glucagon. Reverse transcription-polymerase chain reaction showed the expression of both Ob-Ra and Ob-Rb mRNAs in adrenal cortex and pancreatic islets, the Ob-Rb expression in pancreas being 2-fold higher than in adrenals. Radioimmuno assay demonstrated that leptin enhanced plasma aldosterone and corticosterone concentrations, decreased plasma insulin concentration, and did not significantly affect glucagon plasma concentration. All leptin fragments tested exerted a corticosteroid-hormone secretagogue action, while only leptin fragments 116-130, 138-167 and 93-105 elicited a sizeable insulin antisecretagogue effect. Taken together these findings suggest that: i) the in vivo acute stimulating effect of leptin on adrenocortical hormone secretion is not connected to specific sequences of its molecule, while the insulinostatic effect is probably mediated by the sequence 93-105; and ii) the secretagogue and antisecretagogue effect of leptin are prevalently mediated by Ob-Ra and Ob-Rb, respectively.
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PMID:Acute in vivo effects of leptin and leptin fragments on corticosteroid hormone secretion and entero-insular axis in the rat. 1513 20

ABSTRACT. Despite the high incidence of acute metabolic acidosis, there are no reliable human data to enable physicians to accurately diagnose this disorder. In addition, there is uncertainty about the direction and magnitude of plasma potassium changes in acute metabolic acidosis. The systemic and renal acid-base, electrolyte, and endocrine response to acute acid loads (imposed by three timed NH(4)Cl infusions into the duodenum, 0.9 mmol of NH(4)Cl per kg of body weight over 30 min each) was characterized in six healthy male subjects in whom a metabolic steady-state had been established. Arterialized blood CO(2) tension decreased by 0.85 mmHg per mmol/L decrease in plasma bicarbonate concentration and blood hydrogen ion concentration increased by 0.45 nmol/L per mmol/L decrease in plasma bicarbonate concentration. Plasma potassium did not change significantly (+0.02 +/- 0.02 mmol/L per mmol decrease in plasma bicarbonate concentration). Plasma insulin increased and plasma glucagon levels decreased in acute metabolic acidosis, while catecholamines and aldosterone were not affected significantly. These data provide the first diagnostic criteria for the diagnosis of acute metabolic acidosis in humans. The finding of a hyperinsulinemic response in acute metabolic acidosis suggests that an insulin response counterregulates any acidemia-induced cellular potassium efflux, resulting in stable plasma potassium concentrations.
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PMID:Acute metabolic acidosis: characterization and diagnosis of the disorder and the plasma potassium response. 1515 80


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