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)

In rabbit liver plasma membranes (LPM), specific binding of 125I-insulin rapidly increased in late gestation and peaked at birth, declining thereafter. In contrast, 125I-glucagon binding was lowest in late gestation, somewhat higher at birth, and increased by 48 h although only to 20-25% of adult. These changes in binding were due to changing numbers of receptors involving predominantly high affinity sites for insulin and low affinity sites for glucagon, with only minor changes in affinity. Despite measurable glucagon receptors by birth, fetal LPM produced no increment above basal in cAMP production with maximal doses of glucagon (10(-6) M), prostaglandin E1 (10(-4) M), or epinephrine (10(-4) M). Near birth only NaF (10 mM) produced a modest but significant increment in cAMP. By 2 h postbirth, all stimuli evoked significant increments in cAMP production that increased progressively but was still only 15-20% of adult at 48 h. Furthermore, although specific binding of cholera toxin was greater in fetal LPM (11 +/- 1 vs. 6 +/- 1%), cholera toxin-stimulated cAMP production increased by only 12-26% above basal in the fetus compared with 220% in adult. Markers of membrane purity including 5'-nucleotidase, phosphodiesterase, and insulin or glucagon degradation were not different in fetus and adult. We conclude that receptors and components of the adenylate cyclase complex mature independently; initial coupling occurs between the G/F regulatory protein and the catalytic unit (NaF but not hormonal activation) followed within hours of birth by coupling to the hormone receptor.
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PMID:Ontogeny of hepatic insulin and glucagon receptors and adenylate cyclase in rabbit. 630 5

Some metabolic effects of prostaglandins have been related to their alteration of adenosine-3',5'-monophosphate (cyclic AMP) metabolism in different tissues. Prostaglandins E1 and E2 stimulate liver adenylate cyclase in vitro, but conflicting reports have been made about metabolic changes caused by E prostaglandins in hepatic tissue. We have attempted to resolve these issues by comparing the effects of PGE1 with those of glucagon using broken-cell homogenates, intact hepatocytes, liver slices and perfused liver. Prostaglandin E1 (PGE1) increased cyclic AMP in liver slices and in perfused liver without increasing glycogenolysis, but PGE1 had no discernible effect on carbohydrate or cyclic AMP metabolism in isolated hepatocytes. Glucagon caused predictable increases in cyclic AMP and glycogenolysis using hepatocytes, liver slices or perfused liver. These data can be explained by the absence of PGE effects on cyclic AMP metabolism in hepatocytes. The concentration of E prostaglandins (PGEs) increased 1.75-fold during incubations (37 degrees C) of hepatocyte suspensions, but cyclic AMP remained constant. Addition of exogenous arachidonate and indomethacin to cell suspensions increased and decreased PGEs, respectively, but cyclic AMP and glycogen metabolism were unchanged. Arachidonate and indomethacin likewise did not alter glucagon-stimulated glycogenolysis or cyclic AMP biosynthesis. The production of E prostaglandins and cyclic AMP appears to be unrelated in hepatocytes.
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PMID:Dissociation of E prostaglandin effects on liver glycogenolysis and cyclic AMP levels. 631 5

Accumulation of cyclic AMP in intact cultured pigment epithelial cells was rapidly enhanced by several agonists. These included vasoactive intestinal peptide (100-fold), glucagon (fivefold), thyroid-stimulating hormone (threefold), prostaglandin E1 (24-fold), L-isoproterenol (27-fold), and histamine (fourfold). The rapidity and magnitude of these effects suggest that these agonists may regulate important retinal pigment epithelial cell functions.
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PMID:Agonist effects on the intracellular cyclic AMP concentration of retinal pigment epithelial cells in culture. 631 91

When rat adipocyte membranes had been labeled with [3H]GTP in the presence of a beta-adrenergic agonist, the subsequent [3H]GDP release was stimulated by beta-agonists or agonists (e.g. glucagon and secretin) of other "activatory" receptors involved in activation of adenylate cyclase, but was not stimulated by agonists (e.g. prostaglandin E1 and adenosine) of "inhibitory" receptors involved in cyclase inhibition. On the contrary, agonists of inhibitory receptors were effective in stimulating GDP release from hamster adipocyte membranes that had been labeled via inhibitory alpha 2-adrenergic receptors, but an activatory receptor agonist such as isoproterenol was not. Thus, the guanine nucleotide regulatory protein (Ni) involved in adenylate cyclase inhibition is an entity distinct from the regulatory protein (Ns) involved in cyclase activation, and multiple activatory or inhibitory receptors are coupled to a respective common pool of Ns or Ni. Preactivated cholera toxin added together with NAD enhanced GDP release from rat adipocyte membranes prelabeled with isoproterenol but was without effect on the release from hamster adipocyte membranes that had been labeled with an alpha-agonist. In sharp contrast, the active subunit of islet-activating protein, pertussis toxin, failed to alter GDP release from the former membrane but completely abolished inhibitory agonist-induced stimulation of GDP release from the latter membrane preparation in the presence of NAD. Thus, the site of action of cholera toxin is Ns, while that of islet-activating protein is Ni. The function of Ni to communicate between inhibitory receptors and adenylate cyclase was lost when it was ADP-ribosylated by islet-activating protein.
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PMID:[3H]GDP release from rat and hamster adipocyte membranes independently linked to receptors involved in activation or inhibition of adenylate cyclase. Differential susceptibility to two bacterial toxins. 631 85

This study explores the in vitro modulation of the lipid-filled phenotype of the lipid interstitial cell (LIC) isolated from the developing rat lung. Isolated LIC lose their cytoplasmic lipid droplets when cultured in fetal bovine serum (FBS) but retain their potential for lipid storage, since they rapidly reaccumulate lipid when subcultured in neonatal rat serum (NRS) and to a lesser extent in adult rat serum (ARS). The return of LIC to a lipid-filled state may not represent cell differentiation, since it occurs in the presence of bromodeoxyuridine. NRS contains twice the free fatty acids (FFA) of FBS and ARS, and doubling the FFA concentration of FBS and ARS increases LIC storage lipids. Serum triglyceride (TG) is 10 times higher in ARS and 23 times higher in NRS than in FBS. Since LIC lipoprotein lipase (LPL) activity is in the range of 3T3-L1 adipocytes (0.56 vs. 1.72 units/mg DNA), the LIC has the potential of incorporating serum lipoprotein-triglyceride. The LPL activity of LIC is 9-12 times that of fetal and adult rat lung fibroblasts and 50 times that of human lung, trachea, or skin fibroblasts; LIC are probably a source of endothelial LPL in the developing lung. The response of LIC and ARLF cyclic-AMP to hormones known to influence lipid synthesis or degradation showed that: only LIC responded to glucagon; prostaglandin E1 was a more potent stimulus to LIC; isoproterenol was a more potent stimulus to ARLF; and neither cell responded to ACTH. The unique nature of LIC tends to support further the concept of fibroblast heterogeneity within tissues.
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PMID:In vitro characteristics of the lipid-filled interstitial cell associated with postnatal lung growth: evidence for fibroblast heterogeneity. 631 35

VIP markedly stimulates intracellular cAMP accumulation in the human retinoblastoma Y-79 cell line. cAMP increased about 5-fold above the basal level with 10(-8)M VIP and reached a maximum level (about 70-fold increase) with 2 X 10(-6)M VIP. Glucagon at 6 X 10(-8)M significantly increased cAMP accumulation with a maximal response at 4 X 10(-7)M. Secretin was only effective at micromolar concentrations. Glucagon at 2 X 10(-6)M had a synergistic effect with VIP at 2 X 10(-8)M. Of other substances tested, L-isoproterenol (25-fold increase) and PGE1 (4-fold increase) were most effective. These results demonstrate that VIP and glucagon modulate cAMP accumulation in Y-79 cells and provide a model for studying the effect of these substances on function of neuronal and on malignant cells in vitro.
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PMID:Modulators of cyclic AMP in monolayer cultures of Y-79 retinoblastoma cells: partial characterization of the response with VIP and glucagon. 632

To gain insight into the mechanisms responsible for the impaired glycogenolytic response to glucagon and the diminished ketogenic capacity of newborn guinea pig, we studied the ontogeny of insulin and glucagon receptors, and the responsiveness of the adenylate cyclase complex to glucagon, PGE1, NaF, and cholera toxin in liver plasma membrane from fetal (58 d, late gestation, and 65 d, term) and adult guinea pigs. The number of insulin receptors (x 10(-10) M/L) was least in 58-d fetus (3.0 +/- 0.4; mean +/- SEM) and increased 3-fold in 65 d fetus (8.8 +/- 0.6; P less than 0.01). In adult guinea pig, both insulin receptor number (6.0 +/- 0.7) and average affinity constant (1.20 +/- 0.08 x 10(8) M-1) were significantly lower (P less than 0.01) compared with 65-d fetus. The number of glucagon receptors remained unchanged between 58-d and 65-d fetuses, but both average and high affinity association constants were significantly higher at d 65. In contrast to the lower capacity and affinity of insulin receptors in the adult compared with term fetus, the total glucagon receptor number (x 10(-10) M/L) in adults (7.2 +/- 0.8) was twice that of the 58 d (3.2 +/- 0.2) and 65 d (3.2 +/- 1.0) fetuses. The average affinity constant (x 10(8) M-1) in adult (3.8 +/- 0.2) was, however, significantly lower than the two fetal groups (58 d, 5.0 +/- 0.3; P less than 0.05 and 65 d, 8.1 +/- 1.0; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ontogeny of insulin and glucagon receptors and the adenylate cyclase system in guinea pig liver. 633 Jun 58

Treatment of MDCK cells with glucagon results in decreases in glucagon, NaF and prostaglandin E1-stimulated adenylyl cyclase activities, indicating the occurrence of a heterologous desensitization process. The extent of desensitization was time and glucagon concentration dependent. Maximal desensitization (30-50% decrease in stimulation by various effectors) was obtained by 4 h at 100 nM glucagon. Glucagon also induced homologous desensitization since after treatment, the Kact of glucagon was specifically increased. Treatment of cells with 10 microM 8-bromoadenosine 3':5'-monophosphate or 10 microM forskolin resulted in decreased hormonal (glucagon and prostaglandin E1) stimulation without any decrease in the stimulation by nonhormonal effectors (NaF, forskolin, and guanyl-5'-yl imidodiphosphate). The stimulatory regulator (Ns) of the adenylyl cyclase system was analyzed after desensitization with glucagon and no measurable changes in the apparent levels of the alpha s subunits of Ns or the activity of Ns as assessed by reconstitution of the cyc- S49 cell membrane adenylyl cyclase were detected. Levels of the alpha i subunit of the inhibitory regulator (Ni) were monitored by labeling with [32P]NAD and pertussis toxin. Membranes of glucagon-treated cells showed a 2-fold increase in the amount of alpha i labeled. Addition of pure Ns to glucagon-treated MDCK cell membranes restored full stimulation by NaF but did not restore stimulation by prostaglandin E1 or glucagon. It is concluded that glucagon induces heterologous and homologous desensitization of the MDCK cell adenylyl cyclase. The locus of the heterologous desensitization is at the level of the regulatory components. Decreased stimulation is thought to occur due to either an increase in the levels of Ni or due to altered interactions between the subunits of Ni.
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PMID:Glucagon-induced heterologous desensitization of the MDCK cell adenylyl cyclase. Increases in the apparent levels of the inhibitory regulator (Ni). 653 77

The responsiveness of the membrane bound adenylyl cyclase (AC) system to various hormones and hormone analogues in a transplantable rat Leydig cell tumor (H-540) has been investigated and compared with that of interstitial tissue from normal adult rats. The results can be summarized as follows: The AC of the Leydig cell tumors was stimulated by isoproterenol, epinephrine, norepinephrine, dopamine, glucagon, PGE1, PGF2 alpha and LH/hCG. The AC of the Leydig cell tumors exhibited a much greater response to PGE1 than the AC in normal interstitial tissue (5-fold and 2-fold stimulation, respectively). The AC of the Leydig cell tumours also revealed a somewhat higher response to isoproterenol than the AC of interstitial tissue (2.5-fold and 2-fold, respectively). Adenylyl cyclase in both tissues were equally stimulated by glucagon (2-fold). The LH response in the Leydig cell tumors was only half of that found in normal Leydig cells. This study indicates, that in spite of the fact that tumor Leydig cells respond to LH and produce testosterone, the response pattern of the AC is different from that of normal Leydig cells.
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PMID:A transplantable rat Leydig cell tumor--2. Adenylyl cyclase activation by prostaglandin E1, isoproterenol and glucagon. 654 13

The effect of E-series prostaglandins (PGE) on hepatic glucose metabolism is controversial. This study uses isolated rat hepatocytes and exogenously added PGE analogs or frequent native PGE additions (to compensate for hepatic PGE degradation) to define PGE's effect on hepatic glycogenolysis. 16,16-Dimethyl PGE2, 15(S),15-methyl PGE2, PGE1 and PGE2 all inhibit glucagon-stimulated glycogenolysis. It is concluded that E-series prostaglandins can act directly on the liver to inhibit glycogenolysis.
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PMID:Inhibition of glucagon-stimulated hepatic glycogenolysis by E-series prostaglandins. 658 8


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