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 effect of guanosine on insulin secretion, adenylyl and guanylyl cyclase activities of isolated rat islets of Langerhans was investigated. Guanosine (1-100 micron) inhibited glucose, tolbutamide, theophylline and prostaglandin E2-stimulated insulin secretion although it failed to affect glucagon stimulated secretion. Prostaglandin E2-stimulated adenylyl cyclase activity of islets was inhibited by guanosine although guanosine had no effect on basal, fluoride, glucagon or GTP-stimulated activity. Guanosine markedly decreased basal guanylyl cyclase activity of islets. These results suggest that guanosine may affect insulin release by inhibiting adenylyl and guanylyl cyclase activities in the beta-cell thereby decreasing the intracellular concentrations of cyclic nucleotides. This effect may be important in modulating the secretory response of the islets to a variety of hormonal agents.
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PMID:Effects of guanosine on insulin secretion and adenylyl and guanylyl cyclase activities of isolated rat islets of Langerhans. 1 8

Hepatocarcinogenesis was initiated in rats with diethylnitrosamine (DEN) followed by a selection with 2-acetylamino-fluorene (2-AAF). Portacaval shunt was then performed in order to promote tumor development. Control rats were not submitted to the initiation--selection protocol and were sham-operated. In control rats, adenylate cyclase activity from crude liver membranes was stimulated 7- to 8-fold by maximal doses of glucagon (10(-6) M) or guanyl-5'-yl-imidophosphate [Gpp(NH)p] (10(-3) M), and 17-fold by a maximal (10(-5) M) dose of forskolin. Guanosine-5'-O-(2-thiodiphosphate) inhibited the response to forskolin (-38%) and to low doses of glucagon (-50%). The initiation--selection protocol increased the activity in basal conditions and in response to various stimuli. The portacaval shunt did not modify the activity of the enzyme with respect to basal activity or the response to glucagon. It significantly decreased the response to Gpp(NH)p (-45%) and to forskolin (-27%). The initiation--selection protocol increased the basal activity of the enzyme (+150%) and its response to Gpp(NH)p (+300%). When tumors developed, the activity of the cyclase further increased (+200%) and an inhibitory effect of GTP on the hormone-stimulated enzyme appeared (-40%). From these results, it is concluded that the promotion of hepatocarcinogenesis by portacaval shunt is coupled with modifications in the activity of adenylate cyclase in response to glucagon and guanylnucleotides.
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PMID:Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis in portacaval shunted rats. 174 14

Crude plasma membranes were prepared from the liver of control rats or of rats submitted to an initiation by diethyl-nitrosamine and selection with 2-acetylaminofluorene and carbon tetrachloride (group IS) or of rats submitted to an initiation-selection protocol followed by a promotion with phenobarbital (group IS PB). In control rats, the diterpene forskolin and glucagon stimulated the activity of adenylate cyclase 6- to 7-fold. Guanosine-5'-O-(2-thiodiphosphate) (GDP beta S) inhibited the stimulation by both agents and the non-hydrolyzable GTP analog, guanyl-5'-yl-imidodiphosphate [Gpp(NH)p], potentiated the stimulatory effect of glucagon. In rats of the IS group, no modification of the activity of the liver cyclase was found, except for an increased response to forskolin and glucagon. In the IS PB group, for the rats without tumor, the only effect of adding phenobarbital was to increase the sensitivity of the cyclase to forskolin. In tumoral tissue, the response to Gpp(NH)p, glucagon and forskolin were increased when compared to the surrounding tissue. In contrast to the surrounding tissue, GDP beta S potentiated the stimulatory effect of forskolin. When the affinity of the glucagon receptors for the hormone was measured in binding experiments, no difference was observed among the rats of the various groups, except for a higher affinity in tumoral tissue. Similarly, GTP inhibited the binding of glucagon with the same potency in each group. It is concluded that during hepatocarcinogenesis, the sensitivity of the adenylate cyclase towards glucagon increases secondarily to a better binding of the hormone to its receptor and to an impairment of the inhibitory regulatory site.
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PMID:Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis. 201 30

The incidence of insulin-dependent diabetes (IDDM) in Chinese is much lower than for Western persons. The study was designed to determine whether Chinese children with transient hyperglycemia would develop diabetes as frequently as Western children. Ten children presenting with transient hyperglycemia were investigated using glucagon stimulation test, oral glucose tolerance test (OGTT) and i.v. glucose tolerance test (IVGTT) to estimate pancreatic insulin secretory function. They were followed up for one to three years. Islet cell antibodies and insulin autoantibodies were also measured. During the follow-up period, 2 of the 10 children developed diabetes at 1 month and 1 year, respectively, after the occurrence of transient hyperglycemia. Both of them had lower C-peptide peak level to glucagon stimulation, decreased first phase insulin release to IVGTT and a diabetic sibling. Islet cell antibodies and insulin autoantibodies were all negative except in one of the two children who later developed diabetes. Although it is still premature owing to the small sample size to conclude that Chinese children with transient hyperglycemia are less likely to develop diabetes than Western children, it is advisable to closely follow up those with a family history of IDDM who seem to be at the greatest risk.
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi
PMID:Clinical implication of transient hyperglycemia in childhood. 907 82

We have recently shown an enhanced expression of inhibitory guanine nucleotide regulatory proteins Gi alpha-2 and Gi alpha-3 and their respective mRNA in hearts from DOCA-salt hypertensive rats. However, it is not known whether these changes are due to the expressed hypertrophy or hypertension. The present studies were therefore undertaken to investigate this possibility. Hypertension in Sprague-Dawley rats was induced by the oral administration of the arginine analog N(omega)-nitro-L-arginine methyl ester (L-NAME) in their drinking tap water for a period of 4 weeks. The control rats were given plain tap water only. L-NAME-treated rats showed an enhanced blood pressure (190 +/- 9.23 mm Hg; n = 20) compared to control rats (121 +/- 6.3 mm Hg; n = 20). However, heart to body weight ratio was not different in the two groups. Guanosine 5'-o-(3-thiotriphosphate) (GTPgammaS) stimulated adenylyl cyclase activity in heart membranes from both groups, but the extent of stimulation was significantly decreased in L-NAME-treated rats. Similarly, stimulations exerted by isoproterenol, glucagon, NaF, and forskolin on adenylyl cyclase were also diminished in L-NAME-treated rats. On the other hand, the inhibitory effect of low concentrations of GTPgammaS on forskolin-stimulated enzyme activity was significantly enhanced. The extent of oxotremorine-mediated inhibition of adenylyl cyclase was unaltered in both control and L-NAME-induced hypertensive rats. The levels of Gi alpha-2 and Gi alpha-3, but not of stimulatory guanine nucleotide regulatory protein Gs alpha, as determined by immunoblotting, were significantly augmented in L-NAME-treated rats. Northern blot studies revealed a significant increase in Gi alpha-2 and Gi alpha-3 mRNA with no changes in Gs alpha mRNA. These results suggest that the altered expression of Gi alpha proteins and adenylyl cyclase activity in L-NAME-treated rats may be attributed to hypertension and not to hypertrophy.
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PMID:Nitric oxide synthase inhibition by N(omega)-nitro-L-arginine methyl ester modulates G-protein expression and adenylyl cyclase activity in rat heart. 912 16

The roles of a trimeric GTP-binding regulatory protein, protein kinase A and mitochondria in the regulation of store-activated (thapsigargin-stimulated) Ca2+ inflow in freshly-isolated rat hepatocytes were investigated. Rates of Ca2+ inflow were estimated by measuring the increase in the fluorescence of intracellular fura-2 following the addition of extracellular Ca2+ (Ca2+o) to cells incubated in the absence of added Ca2+o. Guanosine 5'-[gamma-thio]-triphosphate (GTP[S]) and AlF4(-) inhibited the thapsigargin-stimulated Ca2+o-induced increase in cytoplasmic free Ca2+ concentration ([Ca2+]c) and this inhibition was prevented by the Rp diastereoisomer of adenosine 3',5'-(cyclic)phosphoro[thioate]. cAMP, forskolin and glucagon (half-maximal effect at 10 nM) mimicked inhibition of the thapsigargin-stimulated Ca2+o-induced increase in [Ca2+]c by GTP[S], but had little effect on thapsigargin-induced release of Ca2+ from intracellular stores. Azide and carbonyl cyanide p-trifluoromethoxyphenylhydrazone inhibited the thapsigargin-stimulated Ca2+o-induced increase in [Ca2+]c in the presence of increased cAMP (induced by glucagon). In contrast, Ruthenium Red markedly enhanced the thapsigargin-stimulated Ca2+o-induced increase in [Ca2+]c in both the presence and absence of increased cAMP (induced by forskolin and dibutyryl cAMP). It is concluded that, in hepatocytes, protein kinase A regulates the disposition of Ca2+, which enters the cytoplasmic space through store-activated Ca2+ channels, by directing some of this Ca2+ to the mitochondria. The idea that caution should be exercised in using observed values of Ca2+o-induced increase in [Ca2+]c as estimates of rates of agonist-stimulated Ca2+ inflow is briefly discussed.
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PMID:Protein kinase A regulates the disposition of Ca2+ which enters the cytoplasmic space through store-activated Ca2+ channels in rat hepatocytes by diverting inflowing Ca2+ to mitochondria. 949 83

We have recently reported enhanced levels of G(i)alpha proteins in genetic and other experimentally induced models of hypertension, whereas the levels of G(s)alpha were decreased in hypertensive rats expressing cardiac hypertrophy. The present studies were undertaken to investigate whether the decreased levels of G(s)alpha are associated with cardiac hypertrophy per se and used an aortocaval fistula (AV shunt; volume overload) rat model that exclusively expresses cardiac hypertrophy. Cardiac hypertrophy in Sprague-Dawley rats (200-250 g) was induced under anesthesia, and, after a period of 10 days, the hearts were used for adenylyl cyclase activity determination, protein quantification, and mRNA level determination. A temporal relationship between the expression of G(s)alpha proteins and cardiac hypertrophy was also examined on days 2, 3, 7, and 10 after induction of AV shunt in the rat. The heart-to-body-weight ratio (mg/g) was significantly increased in AV shunt rats after 3, 7, and 10 days of induction of AV shunt compared with sham-operated controls, whereas arterial blood pressure was not different between the two groups. Guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) stimulated adenylyl cyclase activity in a concentration-dependent manner in heart membranes from both groups; however, the degree of stimulation was significantly decreased in AV shunt rats. In addition, the stimulatory effects of isoproterenol were also diminished in AV shunt rats compared with control rats, whereas glucagon-stimulated adenylyl cyclase activity was not different in the two groups. The inhibitory effects of oxotremorine (receptor-dependent G(i) functions) and low concentrations of GTPgammaS on forskolin-stimulated adenylyl cyclase activity (receptor-independent G(i) functions) were not different in the two groups. In addition forskolin and NaF also stimulated adenylyl cyclase activity to a lesser degree in AV shunt rats compared with control rats. The levels of G(i)alpha-2 and G(i)alpha-3 proteins and mRNA, as determined by immunoblotting and Northern blotting, respectively, were not different in both groups; however, the levels of G(s)alpha(45) and G(s)alpha(47), and not of G(s)alpha(52), proteins were significantly decreased in AV shunt rats by days 7 and 10 compared with control rats, whereas no change was observed on days 2 and 3 after induction of AV shunt. These results suggest that the decreased expression of G(s)alpha proteins may not be the cause but the effect of hypertrophy and that the diminished responsiveness of adenylyl cyclase to GTPgammaS, isoproterenol, NaF, and forskolin in hearts from AV shunt rats may partly be due to the decreased expression of G(s)alpha. It can be concluded from these studies that the decreased expression of G(s)alpha may be associated with cardiac hypertrophy and not with arterial hypertension.
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PMID:Volume overload cardiac hypertrophy exhibits decreased expression of g(s)alpha and not of g(i)alpha in heart. 1100 79