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)

Techniques of in situ hybridization histochemistry, Northern blot hybridization, and immunocytochemistry were used to investigate the biosynthesis of glucagon-like immunoreactants (GLIs) in rat brain. Cells in the nucleus tractus solitarius of the medulla oblongata of adult rat brain hybridized to a synthetic oligonucleotide probe (GLP-I oligomer) corresponding to nucleotide sequences in pancreatic proglucagon mRNA encoding glucagon-like peptide I (GLP-I), and stained with antisera specific for two antigenic determinants of pancreatic proglucagon, glucagon, and GLP-I. These data suggest that there is de novo synthesis of proglucagon in cells of the nucleus tractus solitarius via expression of a proglucagon mRNA similar to that produced in pancreas. Previous studies have shown that cells in hypothalamus stain with GLP-I antisera, but not with glucagon antisera. However, cells in the hypothalamus did not hybridize with the GLP-I oligomer and may therefore produce a GLP-I immunoreactant that is encoded by a mRNA different from the pancreatic proglucagon-mRNA-encoding glucagon and GLP-I. Northern blot hybridizations with a cDNA probe encoding the entire pancreatic proglucagon sequence did not detect proglucagon/GLP-I mRNAs in polyadenylated RNAs (Poly A RNA) from adult rat brainstem and hypothalamus, probably because of their low abundance. Poly A RNAs from fetal rat brain, however, contained two mRNAs that hybridized to the proglucagon cDNA probe. One mRNA of 1,300 bases is the same size as pancreatic proglucagon mRNA. The second mRNA of 1,500 bases may encode the GLP-I immunoreactant detected in the hypothalamus of adult rat brain. The presence of neurons with glucagon and glucagon-like peptides in the nucleus tractus solitarius suggests a role of these peptides in gustatory and/or cardiopulmonary control.
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PMID:Cellular localization of proglucagon/glucagon-like peptide I messenger RNAs in rat brain. 242 41

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.
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PMID:Proglucagon expression, posttranslational processing and secretion in SV40-transformed islet cells. 255 32

Glucagonlike peptide I (GLP-I-(7-36] is cleaved from proglucagon in ileal epithelial cells and increases in human plasma after nutrient ingestion. This peptide has been shown to stimulate insulin secretion in vitro and in vivo and thus potentially acts as an incretin. To characterize its action on islet cells, the release of insulin, glucagon, and somatostatin by rat pancreatic islet monolayer cultures at varying concentrations of GLP-I-(7-36) was measured. The interaction of GLP-I-(7-36) with nutrient substrates was assessed by adding amino acids and differing glucose concentrations to the cultures. Islet cell cultures (n = 5) were incubated for 1 h in medium containing 1.67 or 16.7 mM glucose or 1.67 mM glucose supplemented with amino acids and GLP-I-(7-36) at 10(-13)-10(-7) M. Hormone release was compared with control cultures containing no GLP-I-(7-36); 1.67-16.7 mM glucose with and without GLP-I-(7-36) at 10(-11) M; and 1.67, 3.3, 8.3, or 11.1 mM glucose alone or supplemented with amino acids, GLP-I-(7-36) 10(-11) M, or both amino acids and GLP-I-(7-36). In medium with 1.67 or 16.7 mM glucose or 1.67 mM glucose and amino acids, GLP-I-(7-36) increased insulin secretion two- to threefold over control at concentrations of 10(-9), 10(-11), and 10(-12) M, respectively. In medium with increasing concentrations of glucose, GLP-I-(7-36) at 10(-11) M significantly increased insulin secretion at glucose concentrations greater than or equal to 3.34 mM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of glucagonlike peptide I-(7-36) on release of insulin, glucagon, and somatostatin by rat pancreatic islet cell monolayer cultures. 257 53

Glucagonlike peptide I (7-37) [GLP-I-(7-37)], encoded with glucagon and glucagonlike peptide II and intervening peptide II in the rat and human glucagon gene, is processed from proglucagon in both pancreas and intestine and is a potent stimulator of insulin secretion. Unequivocal insulin release from the isolated perfused rat pancreas is elicited by a 10(-11) M concentration of this peptide, and a weak response is found at 10(-12) M. We found that GLP-I-(7-37) is approximately 100 times more potent than glucagon in the stimulation of insulin secretion. Insulin release in response to GLP-I-(7-37) is highly dependent on the ambient glucose concentration; no response is detectable at a glucose concentration of 2.8 mM, and at 6.6 and 16.7 mM, insulin release is augmented by 4.7 and 22.8 ng/ml, respectively. The pattern of insulin secretion stimulated by GLP-I-(7-37) is biphasic, with an initial spike followed by a plateau of sustained release. The effects on insulin release of GLP-I-(7-36) amide, a GLP-I analogue, and GLP-I-(7-37) at concentrations of 10(-11) M were indistinguishable. We also found that GLP-I-(7-37) at 10(-9) M does not influence glucagon secretion and that glucagonlike peptide II and the intervening peptide II, two other peptides encoded by the glucagon gene, have no detectable effects on insulin secretion.
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PMID:Glucagonlike peptide I (7-37) actions on endocrine pancreas. 264 90

Glucagon-like peptide 1 amide (GLP-1 amide), a predicted product of the glucagon gene (proglucagon 72-107-amide), and truncated GLP-1 (proglucagon 78-107-amide), recently isolated from porcine small intestine, were infused in doses of 100 and 400 ng/kg/hr and 12.5 and 50 ng/kg/hr, respectively, into eight volunteers to study pharmacokinetics and effects on pentagastrin-stimulated gastric acid secretion (plateau stimulation with pentagastrin at D50: 100 ng/kg/hr). The concentration of GLP-1 in plasma increased from 64 +/- 12 to 189 +/- 23 and 631 +/- 76 pmol/liter, respectively. The concentration of truncated GLP increased from approximately 7 pmol/liter to 28 +/- 3 pmol/liter during the high rate of infusion. A similar increase was seen in response to a mixed meal in eight normal volunteers. The metabolic clearance rate (MCR) of GLP-1 was 2.2 +/- 0.3 and 2.6 +/- 0.3 ml/kg/min, respectively, and the half-life in plasma was 17 +/- 2 min. The MCR of truncated GLP-1 was 13 +/- 2.8 ml/kg/min and the half-life 11.4 +/- 2.1 min. GLP-1 reduced the pentagastrin-stimulated acid secretion 16 +/- 9% during the low-rate infusion and 23 +/- 12% during the high rate (P less than 0.05). Truncated GLP-1 caused a 36 +/- 3% inhibition during the high infusion rate. Thus truncated GLP-1, a naturally occurring peptide, is a potent inhibitor of acid secretion in man and more so than GLP-1.
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PMID:GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans. 271 45

The insulinotropic actions of two forms of glucagon-like peptide 1 (GLP-1) containing 31 and 37 amino acid residues on perfused rat pancreas were compared with that of gastric inhibitory polypeptide (GIP), hitherto the most potent intestinal insulinotropic polypeptide known. The smaller form, C-terminally amidated GLP-1-(7-36), strongly enhanced insulin secretion stimulated by 11.1 mM D-glucose at a concentration as low as 0.1 nM. Comparable effects of GIP and GLP-1-(1-37) on insulin secretion were observed at concentrations of 1.0 nM and 10.0 nM, respectively. At the doses tested, neither GLP-1s nor GIP had any effect on insulin secretion induced by 3.3 mM D-glucose. At a concentration of 1.0 nM, GLP-1-(7-36 amide) also enhanced insulin secretion induced by 5 mM L-arginine whereas at concentrations of up to 10.0 nM, GLP-1-(1-37) did not. The results show that the smaller form of GLP-1 is more strongly insulinotropic than GIP. These findings suggest that the smaller GLP-1 may have a physiologically more important role as a modulator of insulin release.
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PMID:Effect of glucagon-like peptide-1 on insulin secretion. 305 Nov 38

Plasma immunoreactivities of glucagon-like peptide-1 (GLP-1IR) in normal subjects were measured with a specific radioimmunoassay during the arginine tolerance test. Plasma GLP-1IR after arginine infusion showed a 3-fold increase in parallel to plasma glucagon immunoreactivity and plasma glucagon-like immunoreactivity, measured with a glucagon C-terminal specific antiserum (OAL 123) and an N-terminal and/or central region specific glucagon antiserum (OAL 196), respectively. This finding suggested that the increased immunoreactivities of GLP-1 as well as that of glucagon were of pancreatic origin. Upon gel chromatography, plasma at the basal state showed three GLP-1 immunoreactive peaks, eluted in the position of void volume, synthetic GLP-1(72-108), and a smaller molecular fraction. Gel chromatography of plasma after an arginine load showed an additional peak (Mr 13,000-15,000) with little change in other GLP-1 immunoreactive peaks. This large molecular form of GLP-1IR was also shown to exist in the human pancreatic extract. Moreover, the free GLP-1 concentrations in plasma before and after an arginine load were shown to be about equal by reverse phase HPLC. These data suggested that in normal subjects arginine stimulation co-releases GLP-1IR, predominantly large molecular form, with glucogen from the pancreas.
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PMID:A large molecular form of glucagon-like peptide-1 (GLP-1) immunoreactivity is co-released with glucagon from pancreas by arginine in normal subjects. 330 21

Although glucagonlike immunoreactants (GLIs) are present in the central nervous system of several mammalian species, their structural relationship with pancreatic proglucagon is not defined, and their precise anatomical distribution has not been studied extensively. To obtain further information about the structure and biological significance of brain GLIs, the anatomical distribution of three different antigenic determinants of pancreatic proglucagon--glucagonlike peptide I (GLP-I), glucagon, and glicentin--was mapped in the brain of colchicine-treated rats by immunocytochemistry using the avidin-biotin-peroxidase method. Neuronal cell bodies immunoreactive with antisera specific for GLP-I, glucagon, and glicentin were found only in the caudal medulla oblongata. Within the caudal medulla immunostained cell bodies were found at levels from approximately 0.55 mm rostral to the obex to 0.45 mm caudal to the obex, and were located within the nucleus of the solitary tract (NTS) and the dorsal (MdD) and ventral (MdV) parts of the medullary reticular nucleus. The NTS contained three times more immunoreactive cell bodies than the MdD and MdV, and these cell bodies were located in the midline, medial, and lateral subnuclei of the caudal third of the NTS. Immunostaining of the same cell bodies in paired adjacent sections incubated with GLP-I and glucagon antisera or glucagon and glicentin antisera provided evidence for coexistence of the three antigens within the same neurons of the NTS. Nerve fibers and terminals immunoreactive with GLP-I, glucagon, and glicentin antisera were widely distributed throughout the rat brain and there was no discernible difference in the distribution of fibers and terminals immunoreactive with each of the three antisera. The highest densities of immunostained fibers and terminals were observed in the hypothalamus, thalamus, and septal regions, and the lowest in the cortex and hindbrain. The localization of neuronal cell bodies containing GLP-I, glucagon, and glicentin within the NTS and the MdD and MdV, and the extensive distribution of immunoreactive fibers and terminals throughout the rat brain suggest a role for these peptides in the integration of autonomic as well as central nervous system functions.
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PMID:Distribution of glucagonlike peptide I (GLP-I), glucagon, and glicentin in the rat brain: an immunocytochemical study. 338 16

Proglucagon, synthesized in the pancreatic islets and the intestinal L-cells, contains in its precursor structure glucagon, glicentin, and two glucagon-like peptides (GLP-I and GLP-II) separated by an intervening peptide (IP-II). We have cloned a stable rat islet cell line expressing the glucagon gene at high levels, thereby allowing us to study the posttranslational processing of proglucagon in this cell line. In contrast to the processing of proglucagon in the pancreas, in which glucagon is liberated, in the cell line we found the intestinal pattern of peptides consisting of glicentin, at least two forms of GLP-I [GLP-I-(1-37) and GLP-I-(7-37)], GLP-II, IP-II, and an amidated form of IP-II. No individually processed glucagon peptide was detected. GLP-I-(1-37), GLP-I-(7-37), GLP-II, IP-II, and IP-II amide coeluted with their respective synthetic peptide standards on gel filtration and ion exchange chromatography. The existence of a single glucagon gene in the rat genome and indistinguishable glucagon mRNAs in pancreas and intestine indicates that the neoplastic transformation that occurred in these islet cells is associated with a phenotypic switch in the differential posttranslational processing of proglucagon to a pattern that mimics that found in the intestinal cells. These observations further support the hypothesis of a common progenitor for the intestinal (L) and islet (A) cells.
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PMID:Proglucagon processing in a rat islet cell line resembles phenotype of intestine rather than pancreas. 353 50

Recently, a putative hormone, glucagon-like peptide I (GLP I), has been identified in the predicted sequences of the precursors to pancreatic glucagon in human, rat, hamster, and ox. The distribution of GLP I immunoreactivity in canine and feline pancreas and gastrointestinal tract was examined immunohistochemically and was compared with that of two other antigenic determinants of pancreatic pro-glucagon, i.e., glucagon and the NH2 terminus of glicentin. All three determinants occurred in the same population of islet cells in normal pancreas and in pancreas consisting predominantly of islet tissue from dogs with canine pancreatic acinar atrophy. Northern blot analysis of mRNA from the latter tissue, using a rat pre-pro-glucagon complementary DNA probe, revealed a single mRNA species similar in size to the pre-pro-glucagon mRNA detected in fetal rat pancreas. The three antigenic determinants of pancreatic pro-glucagon were co-localized also in intestinal L-cells and in canine gastric A-cells. Canine and feline pancreatic pro-glucagons therefore resemble those identified in other mammals and may also occur in gastrointestinal endocrine cells. Although there is evidence that the GLP I sequence is not liberated from pancreatic pro-glucagon, our results raise the possibility that this putative hormone may be a cleavage product of pro-glucagon in the gastrointestinal tract.
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PMID:Distribution of glucagon-like peptide I in canine and feline pancreas and gastrointestinal tract. 375 50


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