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)

HIT T15 is a B cell line derived from SV40 transformation of hamster islets. We describe here a HIT T15 variant, designated HIT T15-G, which appears to have evolved spontaneously and which expresses glucagon. Regulation of glucagon gene expression, posttranslational processing of proglucagon, and secretion of glucagon were studied in this cell line. Glucagon mRNA concentrations were increased approx. 2-fold following incubation of cells for 18 h in 10 microM forskolin but were unaffected by treatment with a phorbol ester (12-O-tetradecanoylphorbol 13-acetate; TPA) or with ionomycin. Proglucagon was processed to glucagon, and several large molecular weight forms of GLP-I and GLP-II which may include the major proglucagon fragment (MPF). The secretion of glucagon was stimulated by forskolin (5-fold), adrenalin (2-fold), arginine (3-fold) and KCl (2-fold) but was unaffected by glucose. These results suggest that the HIT T15-G cells may represent a less differentiated form of the parental HIT T15 cell line in which A cell phenotype is dominant but not complete.
Mol Cell Endocrinol 1989 Nov
PMID:Proglucagon expression, posttranslational processing and secretion in SV40-transformed islet cells. 255 32

The regenerative and functional capacity of B-cells in the remaining pancreatic tissue after surgical removal of 40%, 60% and 80% of the pancreas was examined in 7 month old pigs (three animals in each group). Prior to resection and 1, 3 and 6 weeks after surgery, basal and glucose-stimulated levels of insulin and blood glucose were determined and compared with the preoperative data and that of sham-operated controls. For quantitative morphology, the volume of the resected specimen and the residual pancreatic tissue, 6 weeks after surgery, was determined and sections evaluated by immunocytochemistry (insulin, glucagon, somatostatin, pancreatic polypeptide) combined with morphometry. In the remaining pancreas, the volume density of the B-cells was increased by 19% (1.57-1.92 after 60% resection; p less than 0.02) and 56% (1.57-2.38 after 80% resection; p less than 0.02) 6 weeks after surgery, compared with the respective resected portion of the pancreas and the controls (n = 12). The non-B-cells gained between 0-10% (PP-cells), 10-20% (D-cells) and 30-40% (A-cells) in the different resection groups. As the number of B-cells per given islet area remained unchanged (mean 4.12 cells/0.25 mm2), the increased volume density was due to an increase in cell number rather than cell size. Insulin secretion (integrated values, 0-120 min), was not significantly impaired after 40% and 60% resection (2711 +/- 250 all preoperative samples; 3215 +/- 474 40% at 6 week intravenous glucose tolerance test (IV-GTT); 1677 +/- 109 60% at 6 week IV-GTT), although the glucose levels (integrated values) were increased during the IV-GTT. The 80% resected animals showed a significant decrease in the insulin response only 1 week after surgery (integrated values: 2711 +/- 250 all preoperative samples, compared with 1250 +/- 508 1 week IV-GTT; p less than 0.05), while the integrated glucose values during IV-GTT (0-120 min) were significantly elevated throughout the observation period. These results suggest a B-cell hyperplasia in the residual pancreas after resection, which may cope with a normal functional demand, but disclose functional abnormalities when challenged with an increased glucose load.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Increase in B-cells in the pancreatic remnant after partial pancreatectomy in pigs. An immunocytochemical and functional study. 256 23

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by the cAMP as well as the calcium and cGMP second messenger systems. Treatment of intact rat PC12 cells with neuropeptides including secretin and vasoactive intestinal polypeptide (VIP) stimulated tyrosine hydroxylase activity 2 to 3-fold in vitro. Secretin (EC50 = 10 nM) was about 3 orders of magnitude more potent than VIP (EC50 = 3 microM). A combination of several protease inhibitors failed to enhance the potency of either peptide. Other members of the secretin family including glucagon and peptide histidine isoleucine (PHI) stimulated tyrosine hydroxylase activity to a lesser extent. Somatostatin, which is not homologous to secretin, was ineffective. The maximal response of tyrosine hydroxylase activation to 1 microM secretin occurred within 6-15 sec. Secretin, VIP, and forskolin also enhanced tyrosine hydroxylase activity (3,4-dihydroxyphenylalanine production) in intact cells, as determined by high performance liquid chromatography and electrochemical detection. Secretin, VIP, PHI, and glucagon increased the levels of cAMP in PC12 cells more than 10-fold, as determined by radioimmunoassay. We also demonstrated that cAMP is released from the cells into the incubation medium following secretin treatment. Secretin and VIP treatment also enhanced the activity of cAMP-dependent protein kinase in a concentration-dependent fashion, as measured subsequently in vitro. Based on the greater potency of secretin in comparison with VIP, PHI, and glucagon, we suggest that the PC12 cells contain a secretin-preferring receptor that increases cAMP levels and brings about an activation of tyrosine hydroxylase activity through the stimulation of cAMP-dependent protein kinase.
Mol Pharmacol 1989 Dec
PMID:Regulation of tyrosine hydroxylase activity in rat PC12 cells by neuropeptides of the secretin family. 257 21

The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), has been isolated and characterized because of its enterogastrone-type effects. It is also named glucose-dependent insulinotropic polypeptide and is actually considered to be the main incretin factor of the entero-insular axis. Besides these well-described effects on gastric secretion and pancreatic beta cells, it also has direct metabolic effects on other tissues and organs, such as adipose tissue, liver, muscle, gastrointestinal tract and brain. In adipose tissue it is involved in the activation and regulation of lipoprotein lipase (LPL); it also inhibits glucagon-induced lipolysis and potentiates the effect of insulin on incorporation of fatty acids into triglycerides. It may play a role in the development of obesity because of the hypersensitivity of adipose tissue of obese animals to some of these actions. In the liver it does not modify insulin extraction, and its incretin effects are due only to the stimulation of insulin secretion and synthesis. It reduces hepatic glucose output and inhibits glucagon-stimulated glycogenolysis. It might increase glucose utilization in peripheral tissues such as muscle. GIP also has an effect on the volume and/or electrolyte composition of intestinal secretion and saliva. The functional importance of its effect on the hormones of the anterior pituitary lobe remains to be established, as it has never been detected in the brain. Its links with insulin are very close and the presence of insulin is sometimes necessary for the greater efficiency of both hormones. GIP can be considered as a true metabolic hormone, with most of its functions tending to increase anabolism.
J Mol Endocrinol 1989 May
PMID:Gastric inhibitory polypeptide: a gut hormone with anabolic functions. 266 79

In-vitro translation of anglerfish islet mRNA revealed three glucagon precursors (preproglucagons): one with Mr 16,000 and two with Mr 14,000. The two Mr 14,000 precursors were well separated upon isoelectric focusing gels (pI values of 7.2 and 7.3), but had identical peptide maps. Translation of hybrid-selected Mr 14,000 preproglucagon mRNA in the presence of microsomal vesicles revealed that both precursors were processed to the same proglucagon. Northern blot analysis detected two mRNA species encoding Mr 14,000 precursor. A full-length Mr 14,000 preproglucagon cDNA was subcloned into a transcription vector, and coupled in-vitro transcription-translation was performed; surprisingly, both Mr 14,000 precursors were synthesized. To test whether acetylation of the free amino terminus generated the more acidic precursor, acetylase activity was partially inactivated with the inhibitor S-acetonyl-CoA, and acetyl-CoA was depleted by addition of oxaloacetate and citrate synthetase. Under these conditions, the level of the most basic preproglucagon was greatly enhanced, but when exogenous acetyl-CoA was added, the acidic form predominated. We conclude that acetylation generates the acidic precursor, and we discuss the implications of our findings for the biogenesis of other peptide hormones.
J Mol Endocrinol 1989 Mar
PMID:In-vitro biosynthesis of multiple preproglucagons results from acetylation of the primary translation products. 267 84

In the mammalian brain, a major regulatory peptide is vasoactive intestinal peptide (VIP). This 28 amino acid peptide, originally isolated from the porcine duodenum, was later found in the central and peripheral nervous systems and in endocrine cells, where it exhibits neurotransmitter and hormonal roles. Increasing evidence points to VIP's importance as a mediator or a modulator of several basic functions. Thus, VIP is a major factor in brain activity, neuroendocrine functions, cardiac activity, respiration, digestion, and sexual potency. In view of this peptide's importance, the mechanisms controlling its production and the pathways regulating its functions have been reviewed. VIP is a member of a peptide family, including peptides such as glucagon, secretin, and growth hormone releasing hormone. These peptides may have evolved by exon duplication coupled with gene duplication. The human VIP gene contains seven exons, each encoding a distinct functional domain on the protein precursor or the mRNA. VIP gene transcripts are mainly found in neurons or neuron-related cells. VIP gene expression is regulated by neuronal and endocrine signals that contribute to its developmental control. VIP exerts its function via receptor-mediated systems, activating signal transduction pathways, including cAMP. It can act as a neurotransmitter, neuromodulator, and a secretagog. As a growth and developmental regulator, VIP may have a crucial effect as a neuronal survival factor. We shall proceed from the gene to its multiple functions.
Mol Neurobiol 1989
PMID:VIP: molecular biology and neurobiological function. 269 76

Gastric inhibitory polypeptide (GIP) is a 42-amino-acid hormone which may have a role in the regulation of insulin secretion. The characterization of cDNA clones encoding this hormone indicates that it is derived by proteolytic processing of a 153-amino-acid precursor. The human gene coding for the human GIP precursor spans approximately 10 kilobase pairs and consists of six exons. Similar to genes encoding other members of the glucagon superfamily, each exon appears to encode a distinct region of the GIP precursor or its mRNA. The promoter region of the human GIP gene contains potential binding sites for a number of transcriptional factors including Sp 1, AP-1, and AP-2. The human GIP gene has been assigned to chromosome 17q21.3----q22.
Mol Endocrinol 1989 Jun
PMID:Gastric inhibitory polypeptide: structure and chromosomal localization of the human gene. 273 53

A model system using a transformed dog kidney cell line (Madin-Darby canine kidney), has been established for studying the process of differentiation. Glucagon responsiveness can be restored to these transformed cells by various differentiation inducers, including prostaglandin E2. Glucagon response was measured in terms of the ability of glucagon to stimulate cAMP production. Induction of glucagon sensitivity seems to be mediated by cAMP. The ability of various prostaglandin analogs to elevate the cAMP level correlates closely with their ability to induce glucagon sensitivity. In fact, 8-Br-cAMP is also a potent inducer. To define the nature of this cAMP-mediated process, we identified several inhibitors of this induction process. These differentiation inhibitors include serum, phorbol ester, and epidermal growth factor. These inhibitors do not have a direct effect on cAMP production by cells in the presence or absence of hormones. Furthermore, induction by 8-Br-cAMP is also inhibited by these agents. Therefore, the site of inhibition is located beyond the point of cAMP production. Possible interaction between cAMP- and epidermal growth factor-dependent phosphorylations is discussed.
Mol Cell Biol 1987 Dec
PMID:Induction of glucagon sensitivity in a transformed kidney cell line by prostaglandin E2 and its inhibition by epidermal growth factor. 283 Apr 89

Some characteristics of adenylate cyclase of catfish (Ictalurus melas) liver membranes were studied, and the effects of catecholamines and of glucagon were tested. The enzyme has an optimum temperature of 40 degrees C, and a Km for ATP of 0.16 mM at 30 degrees C, and requires Mg2+ for its activity. The enzyme activity is inhibited with a Ca2+ concentration higher than 5 X 10(-5) M, and enhanced with F- higher than 10(-4) M. The response of adenylate cyclase to GTP is biphasic, with a maximum of activity at 10(-5) M GTP. Catecholamines (epinephrine, norepinephrine, isoproterenol, phenylephrine) enhance cyclase activity. Propranolol inhibits the increase in enzyme activity induced by catecholamines, whereas phentolamine is ineffective. This indicates that catecholamines (phenylephrine included) activate adenylate cyclase through a beta-adrenergic mechanism. Glucagon (mammalian) has a smaller effect than epinephrine in increasing the enzyme activity of catfish hepatocyte membranes. This fact is the opposite of that observed for the cyclase activity of rat liver membranes.
Mol Cell Endocrinol 1988 Dec
PMID:Adenylate cyclase of catfish hepatocyte membranes: basal properties and sensitivity to catecholamines and glucagon. 285 Sep 55

Specific binding sites for 125I-labelled rat peptide-histidine-isoleucine (PHI) were identified on rat insulinoma-derived RINm5F cells. The concentrations of peptides producing half-maximal displacement of label were rat PHI, 0.36 +/- 0.14 nM, vasoactive intestinal polypeptide (VIP), 0.38 +/- 0.13 nM and secretin, approximately 0.2 microM. Glucagon and glucagon-like peptide-1(7-36)amide were without effect on binding. PHI and VIP produced dose-dependent increases in cAMP production in the cells that were significantly (P less than 0.05) above unstimulated rates for ligand concentrations between 10(-8) and 10(-6) M. Both PHI and VIP produced a small but significant (P less than 0.05) enhancement in the rate of release of immunoreactive insulin from the cells but the effect was not dose dependent.
Mol Cell Endocrinol 1988 Dec
PMID:Binding sites for peptide-histidine-isoleucine (PHI) on rat insulinoma-derived RINm5F cells. 285 Sep 58


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