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 acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0 +/- 0.25 vs 2.4 +/- 0.2 ng AngI/ml/h; p less than 0.01) and glucagon levels (40 +/- 11 vs 20 +/- 16 pg/ml; p less than 0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE2, and PGF2 alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r = 0.7; p less than 0.001) and urinary prostaglandin E2 and glomerular filtration (r = 0.52; p less than 0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.
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PMID:Effect of somatostatin on kidney function and vasoactive hormone systems in health subjects. 168 Nov 32

The renal effect of cyclic somatostatin was studied on healthy subjects. The somatostatin was used at therapeutical dose in intravenous infusion. Somatostatin decreases the renal plasma flow, glomerular filtration rate, osmotic and free water clearances, sodium and potassium excretion and the tubular reabsorption of phosphorus while urinary osmolality increases. Under somatostatin infusion the urinary excretion of catecholamines, PGE2, PGF2 alfa and the plasma renin activity and the plasma concentration of glucagon and growth hormone decrease. The antidiuretic activity of somatostatin is due to a) a direct haemodinamic effect, b) an influence on the renal tubular transport as well and also c) because of change the water handling in the collecting ducts.
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PMID:[Effect of somatostatin on kidney function]. 168 89

Prostaglandins (PG) modulate hepatocyte glucose and lipid metabolism. Hepatocytes rapidly metabolize PG via beta-oxidation, terminating PG action. Clofibrate induces hepatic peroxisomal beta-oxidative activity, for which PG are substrates. To determine the effect of clofibrate-treatment on liver PG metabolism and action, hepatocytes were isolated from rats maintained on a control or clofibrate-supplemented (0.5%) diet for 7 to 9 days. Rates of PG catabolism were determined by high performance liquid chromatography resolution of [3H]PG from [3H]metabolites. Clofibrate treatment enhanced the rates of PGE2, PGF2, and PGD2 degradation by 85%, 278% and 137%, respectively. Rates of PG degradation were correlated with hepatocyte carnitine acetyltransferase activity, a marker of peroxisomal proliferation. Further evidence of enhanced hepatocyte peroxisomal beta-oxidation of PG after clofibrate-treatment was obtained by confirming loss of the 1-position carbon from [1-14C]PGE2 during PGE2 metabolism and failure of the carnitine acyltransferase inhibitor acetyl-DL-aminocarnitine to inhibit PGE2 metabolism. Associated with the faster degradation of PGE2 by hepatocytes from clofibrate-treated rats was loss of inhibition of hepatocyte glucagon-stimulated glycogenolysis by exogenous PGE2. Thus, clofibrate's induction of peroxisomal beta-oxidation is associated with accelerated catabolism of PG and decreased PG action. Alterations in PG breakdown provide a mechanism for modulating hepatic PG effects.
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PMID:Effect of clofibrate treatment on hepatic prostaglandin catabolism and action. 204 19

Prostaglandins (PGs) are known to have effects on hepatic glucose metabolism. Some actions of PGs in intact liver systems may not involve PG effects directly at the level of the hepatocyte. To define the ability of structurally distinct prostaglandins to affect hepatocyte metabolism directly, the regulation of glycogenolysis was studied in hepatocytes isolated from male Sprague-Dawley rats. PGF and PGB2 inhibited glucagon-stimulated glycogenolysis in the hepatocyte system. Pinane thromboxane A2 (PTA2) and PGD2 had no effect on glucagon-stimulated glycogenolysis. Consistent with their inhibition of glucagon-stimulated glycogenolysis, PGF2 and PGF2 alpha inhibited glucagon-stimulated hepatocyte cyclic AMP accumulation. These actions of PGB2 and PGF2 alpha are identical with those previously reported for PGE2. Additionally, PGE2, PGF2 alpha and PGB2 inhibited glucagon-stimulated adenylate cyclase activity in purified hepatic plasma membranes. In contrast, PGF2 alpha, PGD2 and PTA2 were all without affect on basal rates of hepatocyte glycogenolysis or hepatocyte cyclic AMP content. PGE2 also inhibited glycogenolysis stimulated by the alpha-adrenergic agonist phenylephrine. Exogenous arachidonic acid was not able to reproduce the affects of PGE2 or PGF2 alpha on hepatocyte glycogenolysis, consistent with an extra-hepatocyte source of the prostaglandins in the intact liver. Thus PGE2 and PGF2 alpha act specifically to inhibit glucagon-stimulated adenylate cyclase activity. No prostaglandin tested was found to stimulate glycogenolysis. PGE2 and PGF2 alpha may represent intra-hepatic modulators of hepatocyte glucose metabolism.
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PMID:Structural specificity for prostaglandin effects on hepatocyte glycogenolysis. 215 11

Plasma levels of glucagon, secretin, norepinephrine, arginine-vasopressin, and prostaglandin biosynthesis in the gastric mucosa were determined in cirrhotic patients with gastric vascular ectasia associated with hypoacidity, in cirrhotics without this lesion, and in healthy controls. Plasma concentrations of glucagon, secretin, and norepinephrine were similar in cirrhotics with gastric vascular ectasia and cirrhotics without this lesion, these concentrations being significantly higher (p less than 0.05) than in healthy controls. However, there was no significant difference between plasma levels of arginine-vasopressin in patients with cirrhosis (with or without gastric vascular ectasia) and those in healthy controls. The biosynthesis of prostaglandin E2 in the antrum of the gastric mucosa was significantly higher in cirrhotics with gastric vascular ectasia than in cirrhotics without this lesion (p less than 0.05) and healthy controls (p less than 0.005). Prostaglandin E2 in the corpus was significantly higher (p less than 0.05) in cirrhotics with gastric vascular ectasia than in healthy controls. The biosynthesis of 6-keto PGF1 alpha (a stable metabolite of prostacyclin) and PGF2 alpha in the corpus and antrum of gastric mucosa was not significantly different in cirrhotics with gastric vascular ectasia, cirrhotics without this lesion and healthy controls. Since prostaglandin E2 has a vasodilator and acid-inhibitory effect, we speculate that high content of this prostanoid in the gastric mucosa may play a role in the pathogenesis of ectatic capillaries and acid inhibition present in some cirrhotic patients.
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PMID:Increased gastric PGE2 biosynthesis in cirrhotic patients with gastric vascular ectasia. 230 36

E series prostaglandins and their biologically active analogue, 16,16-dimethylprostaglandin E2 (dimethylprostaglandin E2), have inhibited hormone-stimulated glycogenolysis in hepatocytes cultured from male rats (Okumura, T., Sago, T. and Saito, K. (1988) Biochim. Biophys. Acta 958, 179-187). However, in the case of female rat hepatocytes, it is evident that dimethylprostaglandin E2 did not inhibit the glycogenolysis stimulated by glucagon, isoproterenol (beta-adrenergic response) or epinephrine (with propranolol, alpha 1-adrenergic response) in cultures on day 1. Dimethylprostaglandin E2 inhibited such hormone-stimulated glycogenolysis in cultures on day 2 and 3, but to a lesser extent than in the male-derived cells. The concentration for 50% inhibition was approx. 10(-8) M; inhibition was completely blocked by a pertussis toxin. Prostaglandin E2 had the same effect as dimethylprostaglandin E2; prostaglandins D2 and F2 alpha had no effect. Additions of sex hormones, 17 beta-estradiol and testosterone, and palmitic acid (diminishing the prostaglandin catabolism) to the culture medium did not change the effect of dimethylprostaglandin E2. These data indicate that a sex difference exists in the inhibition of hepatic glycogenolysis by prostaglandin E2 and its analogue in rat cultured hepatocytes, although the factor causing such a difference is a present unknown.
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PMID:A sex difference in the effect of prostaglandins on hormone-stimulated glycogenolysis in primary cultures of rat hepatocytes. 231 Jul 80

The involvement of endogenous prostaglandins (PGs) in pancreatic endocrine and exocrine secretion was investigated, using the isolated and perfused dog pancreas. Spontaneous production of both PGE2 and 6-keto-PGF1 alpha was recorded in venous effluent. Prostaglandin production increased following stimulation with both 10 x 10(-11) and 20 x 10(-11) mol of CCK-8, but was not affected by a 5 x 10(-11) mol infusion. Insulin, glucagon, and amylase release was stimulated by 10 x 10(-11) mol of CCK-8. Indomethacin pretreatment with 10 mg/kg totally abolished endogenous PG production, but failed to suppress an insulin and glucagon response. On the other hand, an amylase response was accelerated by indomethacin pretreatment. Although low dose CCK-8 failed to stimulate endogenous prostaglandin production, a brisk exocrine secretion was not suppressed by indomethacin pretreatment. From the above results, we conclude that endogenous PGs do not appear to play an important role in pancreatic endocrine and exocrine secretion, but might have a cytoprotective effect on the pancreatic acinar cells damaged by CCK-8.
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PMID:Involvement of endogenous prostaglandins in pancreatic endocrine and exocrine secretion in dog pancreas. 247

E-series prostaglandins (PGs) inhibit glucagon-stimulated cyclic AMP accumulation in hepatocytes as well as glucagon-stimulated glycogenolysis and fatty acid oxidation. The present study was designed to test the hypothesis that this inhibition occurs via interactions with a plasma membrane PGE2 receptor coupled to adenylate cyclase. PGE2 receptors in rat liver plasma membranes were examined using competitive binding studies [( 3H]PGE2 vs. PGE1). Binding data were analyzed to determine the number of apparent binding sites and the PGE dissociation constant (Kd) at each site. Rat liver plasma membranes contained two classes of binding sites with Kd values of 9.9 X 10(-10) and 8 X 10(-9) M. Addition of the GTP-analog guanyl-5'-6'-imidodiphosphate (0.1 mM) altered the PGE2 binding such that a single class of sites with low affinity (Kd = 4 X 10(-9) M) was observed. Similarly, liver plasma membranes isolated from rats pretreated with pertussis toxin contained only a single class of PGE2 binding sites in the absence of guanyl-5'-6'-imidodiphosphate (Kd = 3.4 X 10(-9) M). PGE2 (10(-10) M) inhibited liver membrane adenylate cyclase activity stimulated by forskolin (by 57%) and glucagon (by 24%). This inhibition was not observed in membranes isolated from rats treated with pertussis toxin. Thus, the present studies demonstrate that PGE binding to its hepatic receptors is regulated by a pertussis toxin sensitive guanine nucleotide binding protein coupled to inhibition of adenylate cyclase.
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PMID:Coupling of hepatic prostaglandin receptors to adenylate cyclase through a pertussis toxin sensitive guanine nucleotide regulatory protein. 253 66

alpha 2-Adrenoceptor agonists inhibit glucose-stimulated insulin release and glucose utilization in pancreatic islets. In isolated pancreatic islets of the rat, the Ca2+ channel agonists CGP-28392 and BAY-K-8644 increased insulin release in the presence of clonidine. Neither CGP-28392 nor BAY-K-8644 antagonized the effect of clonidine on glucose utilization. The Ca2+ ionophore, ionomycin, also did not affect glucose utilization in the presence or absence of clonidine. Glucagon partly reversed the effects of clonidine on insulin release, and it potentiated glucose-stimulated insulin release in the absence of clonidine. Glucagon reversed the effects of clonidine on glucose utilization. Amiloride antagonized the effects of clonidine on insulin secretion but did not enhance markedly glucose utilization in the presence or absence of clonidine. Carbamylcholine and arecoline reversed the effects of clonidine on glucose utilization and partly reversed the effects on insulin release in the absence of extracellular Ca2+. Prostaglandin (PG) E2, but not PGF2 alpha, inhibited glucose utilization in a time- and concentration-dependent manner. PGE2 also inhibited glucose-stimulated insulin release. Pertussis toxin blocked both actions of PGE2. The cyclooxygenase inhibitor indomethacin did not affect insulin release or glucose utilization in the presence of clonidine. Thus, elevated intracellular Ca2+ levels antagonize the effects of clonidine on insulin release, whereas other mediators appear to be required to alter glucose utilization.
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PMID:Calcium mobilization, prostaglandin E2 and alpha 2-adrenoceptor modulation of glucose utilization and insulin secretion in pancreatic islets. 254 83

Several prostaglandins inhibit the cAMP response to glucagon and beta-adrenergic stimulation in hepatocytes. To probe the mechanism of this inhibition, we have examined in primary hepatocyte cultures how pretreatment with pertussis toxin (islet-activating protein) influences the ability of the cells to respond to hormones and prostaglandins. Pertussis toxin augmented the effects of glucagon, epinephrine and isoproterenol, and also markedly enhanced the cAMP response to prostaglandin E1 (PGE1). Furthermore, whereas PGE1, PGE2, PGI2 and PGF2 alpha attenuated the cAMP responses to glucagon in control cultures, this inhibition was abolished in cells pretreated with pertussis toxin. A more detailed comparison was made of the effects of PGE1 and PGF2 alpha. In cells not treated with pertussis toxin, both these prostaglandins at high concentrations reduced the cAMP response to glucagon and isoproterenol by approximately 50%, but dose-effect curves showed that PGE1 was about 100-fold more potent as an inhibitor than PGF2 alpha. Pertussis toxin abolished the inhibitory effects of PGE1 and PGF2 alpha with almost identical time and dose requirements. The results obtained with PGE1, PGE2, PGI2 and PGF2 alpha suggest that prostaglandins of different series attenuate hormone-activable adenylate cyclase in hepatocytes through a common mechanism, dependent on the inhibitory GTP-binding protein.
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PMID:Pertussis toxin abolishes the inhibitory effects of prostaglandins E1, E2, I2 and F2 alpha on hormone-induced cAMP accumulation in cultured hepatocytes. 283 60


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