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)

Cyclic AMP-dependent protein kinase subunit expression was studied during the first 35 h of primary culture of hepatocytes isolated from rats fed a protein restricted diet. In the absence of elevated cAMP the ratio between regulatory (RI + RII) and catalytic (C) subunits was constant. There was an increase of RI and a decrease of RII, the RI/RII ratio rising from 1 to 2.4 during the 35 h of culturing studied. This disproportionate expression of RI was reflected in an increase of RI alpha mRNA relative to RII alpha mRNA. The increase of liver RI previously noted after amino acid feeding of protein starved rats was thus reproduced when hepatocytes from such animals were cultured in an amino acid rich medium. When the cell cAMP level was chronically elevated by adding glucagon/isobutylmethylxanthine at the time of seeding, the C level decreased by more than 50% in a few hours. The concentration of C alpha mRNA was not affected. The elevated cAMP also led to a transient increase of RI alpha- and RII alpha mRNA. The effects of glucagon could be reproduced by cAMP analogs. The cAMP-induced down-regulation of C without concomitant down-regulation of R led to an increased R/C ratio. The decreased C and the increased R/C ratio both ensure that the hepatocytes will show a reduced kinase activation in response to a second challenge with cAMP (i.e. show hysteresis).
Mol Endocrinol 1990 Mar
PMID:The expression of cAMP-dependent protein kinase subunits in primary rat hepatocyte cultures. Cyclic AMP down-regulates its own effector system by decreasing the amount of catalytic subunit and increasing the mRNAs for the inhibitory (R) subunits of cAMP-dependent protein kinase. 216 Jun 3

Glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) is a potent stimulator of insulin secretion. Receptors for this hormone have been found on different insulinoma-derived cell lines, e.g. the RINm5F cell line which is derived from a radiation-induced rat insulinoma. To characterize the part of the GLP-1(7-36)amide molecule that is responsible for binding to its receptor on RINm5F cells, binding studies with synthetic C-terminal (GLP-1(21-36)amide) and synthetic N-terminal (GLP-1(7-25] GLP-1 fragments were carried out. GLP-1(21-36)amide showed dose-dependent binding to the GLP-1(7-36)amide receptor but was approximately 1500 times less potent in inhibiting binding of 125I-labelled GLP-1(7-36)amide than the intact hormone. GLP-1(7-25) at concentrations up to 10 mumol/l did not inhibit binding of label. Neither fragment changed intracellular cyclic AMP concentrations, in contrast to GLP-1(7-36)amide which increased intracellular cyclic AMP. GLP-1(21-36)amide, however, acted as a weak partial antagonist of GLP-1(7-36)amide with respect to GLP-1(7-36)amide-dependent stimulation of cyclic AMP production.
J Mol Endocrinol 1990 Aug
PMID:Glucagon-like peptide-1(7-36)amide: characterization of the domain responsible for binding to its receptor on rat insulinoma RINm5F cells. 216 8

We had reported earlier the enhanced phosphorylation of a 38-kilodalton protein (p38) in rat liver plasma membrane by ras proteins. Now we show that glucagon increased the phosphorylation of the same protein. The nature and site(s) of phosphorylation were the same as those for the ras proteins. Both ATP and GTP could donate phosphate for the phosphorylation of p38. The stimulation of p38 phosphorylation by glucagon was guanine nucleotide dependent. This observation, together with our data on the stimulation of p38 phosphorylation by AIF4-, suggest the involvement of G proteins in the reaction. We also showed that glucagon stimulates the phosphorylation of p38 in vivo.
Mol Cell Biol 1990 Jun
PMID:Glucagon and p21 ras enhance the phosphorylation of the same 38-kilodalton membrane protein from rat liver cells. 218 88

Glucagon and the glucagon-like peptides are encoded within a larger precursor, proglucagon. Transcription of the glucagon gene in pancreas, intestine, and brain gives rise to identical proglucagon mRNA transcripts, after which tissue-specific post-translational processing produces different profiles of proglucagon-derived peptides in each tissue. The importance of glucagon gene 3'-untranslated and 3'-flanking sequences in the control of glucagon mRNA production was studied by transfecting a series of 3'-deleted glucagon genes into fibroblast and islet cell lines. Glucagon genes containing 2 kilobases of 3'-flanking sequences gave rise to accurately processed mRNA transcripts in both baby hamster kidney fibroblasts and InR1-G9 islet cell lines. Deletion of all but 50 basepairs of 3'-flanking sequence had no effect on glucagon mRNA 3'-end formation. In contrast, additional deletion of 3'-flanking and 3'-untranslated sequences resulted in the production of read-through mRNA transcripts with aberrant 3'-ends. The results of these studies define a 50-basepair region in the 3'-flanking sequence of the glucagon gene important for the accurate processing of proglucagon mRNA transcripts.
Mol Endocrinol 1990 Jun
PMID:Glucagon gene 3'-flanking sequences direct formation of proglucagon messenger RNA 3'-ends in islet and nonislet cells lines. 223 38

The degu, Octodon degus, is a South American hystricomorph rodent that is of interest because it develops spontaneous diabetes mellitus and has been found to have islet amyloidosis. To help clarify these problems we have cloned cDNAs encoding islet amyloid polypeptide (IAPP), insulin, and glucagon precursors from this species. The predicted amino acid sequence of degu IAPP is very similar to that of nonamyloid-forming guinea pig IAPP. In contrast, degu insulin and the C-terminal region of degu glucagon are highly divergent from those of other mammals, as is also the case in the guinea pig, suggesting the existence of some form of positive evolutionary pressure on these hormones of carbohydrate metabolism in the hystricomorph rodents.
Mol Endocrinol 1990 Aug
PMID:Cloning of complementary DNAs encoding islet amyloid polypeptide, insulin, and glucagon precursors from a New World rodent, the degu, Octodon degus. 229 24

Knowledge of the metabolic changes that occur in insulin-resistant type 2 diabetes is relatively lacking compared to insulin-deficient type 1 diabetes. This paper summarizes the importance of the C57BL/KsJ-db/db mouse as a model of type 2 diabetes, and illustrates the effects that insulin-deficient and insulin-resistant states have on hepatic glycogen metabolism. A longitudinal study of db/db mice of ages 2-15 weeks revealed that significant changes in certain parameters of hepatic glycogen metabolism occur during this period. The liver glycogen levels were similar between diabetic and control mice. However, glycogen particles from db/db mice were on average smaller in mass and had shorter exterior and interior chain lengths. Total phosphorylase and phosphorylase a activities were elevated in the genetically diabetic mice. This was primarily due to an increase in the amount of enzymic protein apparently the result of a decreased rate of degradation. It was not possible to find a consistent alteration in glycogen activity in the db/db mice. Glycogen synthase and phosphorylase from diabetic liver revealed some changes in kinetic properties in the form of a decrease in Vmax and altered sensitivity to inhibitors like ATP. The altered glycogen structure in db/db mice may have contributed to changes in the activities and properties of glycogen synthase and phosphorylase. The exact role played by hormones (insulin and glucagon) in these changes is not clear but further studies should reveal their contributions. The db/db mouse provides a good model for type 2 diabetes and for fluctuating insulin and glucagon ratios.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1990 Feb 09
PMID:Hepatic glycogen metabolism in the db/db mouse. 240 41

Vasoactive intestinal peptide (VIP) was originally isolated from porcine duodenum and considered to be a gut hormone. Recent evidence indicates that it may also be involved in reproductive functions. In this study, a possible action of VIP on steroidogenesis by cultured testicular cells was investigated. Neonatal testicular cells were treated in vitro with hormones for 3 days and medium steroid or cAMP content was measured by radioimmunoassay. Treatment of cultured cells with VIP (10(-9) to 10(-6) M) increased the production of testosterone, progesterone, and pregnenolone in a dose-dependent fashion. Testosterone production in response to 10(-6) M VIP was about 5-10% of that maximally induced by LH. Addition of methyl-isobutyl-xanthine, a phosphodiesterase inhibitor, to the VIP-containing cultures significantly enhanced production of testosterone by 13-fold, of progesterone by 9-fold, and of pregnenolone by 2.5-fold as compared to treatment with VIP alone. Additional experiments also showed a dose-dependent stimulation of cAMP production by VIP. The VIP-related hormones PHM-27, secretin, and glucagon also stimulated progesterone and testosterone production with a potency order (PHM-27 greater than secretin greater than glucagon) consistent with that observed for other VIP receptor-mediated actions. A direct stimulatory effect of VIP on Leydig cells was indicated in studies on steroidogenesis by testicular cells separated on a metrizamide density gradient. In these studies, VIP stimulated androgen production in an LH-responsive subpopulation of testis cells but failed to affect steroid production in non-LH-responsive cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1986 Nov
PMID:Vasoactive intestinal peptide stimulates androgen biosynthesis by cultured neonatal testicular cells. 243 Aug 45

The glycoprotein hormone alpha-gene is preferentially expressed in placental cell lines, but it is also expressed in several other cell lines indicating that the differential activity of the alpha-gene regulatory elements in various cell types is more quantitative than qualitative. The 5'-flanking region of the alpha-gene contains several distinct DNA regulatory sequences including an upstream regulatory element [(URE) -181 to -150 base pairs (bp)] that stimulates basal expression and an 18 bp twice-repeated cAMP-responsive element [(CRE) -146 to -111 bp]. We constructed an array of fusion genes containing the URE and/or the CRE linked to different truncated promoters [alpha-gene, somatostatin (SRIF), glucagon, Simian Virus 40]. These constructions were transiently expressed in placental, fibroblast, or islet cell lines to identify regulatory sequences involved in cell-specific expression as well as interactions between the URE, the CRE, and different promoter elements. The URE, CRE, and alpha-promoter elements contribute approximately 3-, 6-, and 5-fold, respectively, to preferential expression in JEG-3 cells. In JEG-3 cells, the URE is strictly dependent on the CRE for activity, but it functions in a promoter-independent manner. In contrast, the CRE is markedly promoter dependent. When linked to heterologous enhancers, the alpha-promoter is more active in JEG-3 cells than in other cell lines, thereby contributing substantially to preferential expression in placental cells. Although the CREs derived from the alpha and SRIF genes both activate expression of the alpha promoter, only the alpha CRE activates the SRIF promoter in JEG-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 May
PMID:Enhancer and promoter element interactions dictate cyclic adenosine monophosphate mediated and cell-specific expression of the glycoprotein hormone alpha-gene. 247 27

125I-Labelled glucagon-like peptide-1(7-36)amide was cross-linked to a specific binding protein in plasma membranes prepared from RINm5F rat insulinoma-derived cells using disuccinimidyl suberate. Consistent with the presence of a single class of binding site on the surface of intact cells, only a single radiolabelled band at Mr63,000 was identified by SDS-PAGE after solubilization of the ligand-binding protein complex. The band was not observed when 10nM glucagon-like peptide-1(7-36)amide was included in the binding assay, but 1 microM concentrations of glucagon-like peptide-1(1-36)amide, glucagon-like peptide-2 and glucagon did not decrease the intensity of labelling. No change in the mobility of the band was observed under reducing conditions, suggesting that the binding protein in the receptor is not attached to other subunits via disulphide bonds. In control incubations using plasma membranes from pig intestinal epithelial cells, which do not contain specific binding sites for glucagon-like peptide-1(7-36)amide, no cross-linked ligand-binding protein complex was observed.
J Mol Endocrinol 1989 Mar
PMID:Characterization of the receptor for glucagon-like peptide-1(7-36)amide on plasma membranes from rat insulinoma-derived cells by covalent cross-linking. 255 26

The relationship between stimulation of single C-cells (rMTC-6-23 cell line) with extracellular calcium, glucagon or 8-bromo-cAMP and fluctuations of intracellular free calcium concentration was studied. After pretreatment of rMTC cells with either 1 microM glucagon (30-60 min) or 1 mM 8-bromo-cAMP (5 min) [Ca2+]i started to oscillate when extracellular calcium was raised to 3 mM. These fluctuations in [Ca2+]i could be stopped by chelating the external calcium with EGTA or by adding calcium channel blockers. The voltage-dependent calcium channels in the plasma membrane seem to play a major role in maintaining the oscillations of [Ca2+]i.
Mol Cell Endocrinol 1989 Jul
PMID:Rhythmic oscillations of cytosolic free calcium in rat C-cells. 255 59


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