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)

Adenylate cyclase activity was measured on membrane fractions from the gill epithelium of rainbow trout Salmo gairdneri. Basal and glucagon-stimulated activities responded negatively to homologous neurohypophyseal peptides (arginine-vasotocin and isotocin). This inhibitory effect was totally abolished in the presence of pertussis toxin (IAP). The guanine nucleotide dependence of the enzyme was further explored by using GTP, GDP, and their stable analogs Gpp(NH)p, GTP gamma S, and GDP beta S. The results suggest that neurohypophyseal peptides at low concentrations inhibit the adenylate cyclase system directly by way of a Gi-protein, thus implying the intervention of a new type of membrane receptor for these hormones in fish gills.
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PMID:Gi protein mediates adenylate cyclase inhibition by neurohypophyseal hormones in fish gill. 148 May 12

Islet-activating protein (IAP, a Bordetella pertussis toxin) was employed to test the hypothesis that the inhibitory GTP-binding regulatory protein of adenylate cyclase (Ni) mediates GTP effects on the binding of Ca2+-mobilizing hormones to liver plasma membranes and is involved in calcium mobilization stimulated by these agonists. IAP added to normal liver plasma membranes catalyzed the incorporation of radioactivity from [32P]NAD into a 41,000-Da peptide (presumably the alpha-subunit of Ni). However, no such incorporation was observed in liver membranes prepared from rats 24 hr after intraperitoneal injection of IAP. Angiotensin II attenuated glucagon-stimulated increases in cAMP in hepatocytes prepared from control but not IAP-treated rats. In contrast, following IAP treatment, no changes were observed in the ability of glucagon, vasopressin, angiotensin II, or epinephrine to activate phosphorylase; nor did this treatment alter [3H]vasopressin binding or epinephrine displacement of [3H]prazosin binding. However, IAP treatment decreased [3H]angiotensin II binding affinity when studies were performed in the absence but not the presence of 5'-guanylylimidodiphosphate (GppNHp). This shift was small and represented only 5-8% of the shift in apparent Kd elicited by GppNHp in untreated membranes. In vitro studies with IAP confirmed the results of the radioligand binding studies using in vivo IAP treatment. The effects of NaCl on [3H]angiotensin II binding were also tested but were not typical of other receptors which couple to Ni. The data suggest that, although a small population of hepatic angiotensin II receptors couple to Ni and attenuate glucagon-stimulated increases in cAMP, vasopressin, alpha 1-adrenergic, and the majority of angiotensin II receptors do not interact significantly with Ni. Thus, although there is evidence that agonist-induced Ca2+ mobilization requires a GTP-binding regulatory protein, this protein does not appear to be Ni in rat liver.
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PMID:Effect of islet-activating pertussis toxin on the binding characteristics of Ca2+-mobilizing hormones and on agonist activation of phosphorylase in hepatocytes. 300 28

The role of beta-adrenoceptor regulation in the mechanisms controlling beta-adrenergic responsiveness in hepatocytes was explored, using primary monolayer cultures. When plated in vitro, these cells gradually acquire a strong catecholamine-sensitive adenylate cyclase activity and an enhanced ability to bind the beta-adrenoceptor ligand [125I]iodocyanopindolol (125ICYP). Examination of the time course showed that the increase in the number of 125ICYP binding sites was detectable within 1-2 h of culturing and slightly preceded the elevation of isoproterenol-responsive activity. Then the responsiveness rose steeply and between about 5-24 h it closely followed the increase in beta-receptor binding. Addition of isoproterenol (10 microM) to cells after 20 h of culturing caused a rapid homologous desensitization of the adenylate cyclase (50% after about 5 min). This was paralleled by a down-regulation of beta-adrenoceptors measured both in membrane particles and in total cell lysates. Removal of isoproterenol led to a resensitization of the adenylate cyclase, which was rapid and protein-synthesis-independent after a brief (10-min) desensitization, or slow and cycloheximide-sensitive after prolonged (4-h) exposure to the agonist. In both cases an up-regulation of the 125ICYP binding paralleled the recovery from refractoriness. In contrast, no concurring changes in 125ICYP binding were measured when the beta-adrenoceptor-linked adenylate cyclase activity was enhanced by pretreatment with pertussin toxin (islet-activating protein, IAP) or was desensitized by exposure of the cells to glucagon or 8-bromo-cAMP; however, these modulations of the adenylate cyclase were nonselective, since the pretreatments with IAP, glucagon or 8-bromo-cAMP affected both isoproterenol-sensitive and glucagon-sensitive activities. The results suggest that, in hepatocytes, regulation at the beta-adrenoceptor level is a major determinant for both short-term and long-term selective changes of the beta-adrenergic responsiveness.
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PMID:The relationship between beta-adrenoceptor regulation and beta-adrenergic responsiveness in hepatocytes. Studies on acquisition, desensitization and resensitization of isoproterenol-sensitive adenylate cyclase in primary culture. 303 Jul 43

The influences of IAP on the residual pancreatic endocrine function and carbohydrate metabolism after extensive pancreatectomy in the rat were studied with oral glucose tolerance test (OGTT), arginine tolerance test (ATT), and measurement of hepatic glycogen, and hepatic glycolytic enzyme activity, and histological examination, etc. Wistar male rats weighing around 300 g were divided into the groups with IAP treatment and without it, and in the group with IAP treatment IAP 10 micrograms/kg was administered without anesthesia via the tail vein. In each group 60 and 90% pancreatectomies were performed in accordance with Scow's method, and the simple laparotomy group was used as control. Slight abnormality of glucose tolerance was shown in 60% pancreatectomy. The abnormality became worse with time in 90% pancreatectomy. Glucagon secretion was not damaged markedly even after extensive pancreatectomy. IAP stimulated IRI secretory response and improved glucose tolerance in 60% pancreatectomy group. IAP showed no effect in 90% pancreatectomy group. IAP did not stimulate IRG secretory response after pancreatectomy. Hepatic glycolytic enzyme activity was high in the group with IAP treatment. From the above observation, it has been suggested that IAP may be indicated for the abnormal carbohydrate metabolism after pancreatectomy, if pancreatectomy is not too extensive.
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PMID:[Experimental study on carbohydrate metabolism and pancreatic endocrine function after pancreatectomy--influence of islet activating protein (IAP)]. 396 25

The loss of pancreatic parenchyma resulting from pancreatic resection causes an extreme disruption of glucose homeostasis known as pancreatogenic diabetes. This form of glucose intolerance is different from the other forms of diabetes mellitus in that affected individuals suffer frequent episodes of iatrogenic hypoglycemia. The development of sophisticated surgical procedures, improved postoperative care, and the capacity for early diagnosis of disease has prolonged life expectancy after pancreatic resection. For this reason, pancreatogenic diabetes is now attracting attention as the primary factor influencing quality of life in patients who have undergone this procedure. The incidence of new-onset diabetes mellitus after pancreatic resection increases as the follow-up period after surgery becomes longer and is related to the progression of underlying disease, the type of surgery, and the extent of resection. The pathophysiology of pancreatogenic diabetes is related to pancreatic hormone deficiency and the altered responses of the liver and peripheral organs to lower than normal hormone levels. Hyperglycemia occurs when the amount of insulin produced or administered is insufficient because of unsuppressed hepatic glucose production secondary to a deficiency in pancreatic polypeptide. In contrast, patients lapse into hypoglycemia when insulin is barely excessive because of enhanced peripheral insulin sensitivity and glucagon deficiency. Nutritional state, pancreatic exocrine function and intestinal function also affect glycemic control. Insulin replacement is considered to be the main treatment option for insulin dependent pancreatogenic diabetes. Pancreatic polypeptide replacement and islet autotransplantation have potential as new approaches to treating patients with pancreatogenic diabetes after pancreatic resection. and IAP.
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PMID:Pancreatogenic diabetes after pancreatic resection. 2173 30