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At least 19 recordsLinked to original sources

PubMed1980

Effects of glicentine on insulin secretion.

The glucagon-like immunoreactivity of the gastrointestinal tract is heterogeneous, probably including several different peptides. One of these peptides, glicentine, has recently been extracted and highly purified. Furthermore, by immunocytochemistry a glicentine-like peptide has been reported to occur in the glucagon cell of the pancreatic islets. In the present study we investigated the effects of pure glicentine on insulin release in vivo in mice. The effects were compared with effects of two other peptides, glucagon and GIP. It was found that glicentine had no influence on basal insulin secretion. This was in contrast to equimolar doses of glucagon and GIP, which both stimulated the secretion of insulin. Glucose-induced insulin release was partially inhibited by glicentine. D-glucose, in a dose selected to give a response of 25% of its maximal, raised the plasma insulin concentrations by 44.0 +/- 5.9 microU/ml. The corresponding rise for glicentine plus D-glucose was 22.3 +/- 3.7 microU/ml, i.e. glicentine inhibited glucose-induced insulin released by about 50% (p < 0.01). GIP, on the other hand, enhanced glucose-induced insulin release. This enhancement was diminished by glicentine, a reflection of the inhibition by glicentine of the glucose-induced insulin release. Neither glicentine nor GIP in the doses tested had any effect on insulin secretion induced by cholinergic stimulation. In conclusion, glicentine seems to have no effect on basal insulin release in the mouse, but it partially inhibits glucose-induced insulin secretion. Thus, if the recently demonstrated glicentine-like peptide in the glucagon cell is authentic glicentine, the glucagon cell of the pancreatic islets may contain peptides with stimulatory (glucagon) as well as inhibitory (glicentine) effects on insulin secretion induced by glucose.

Animals↗

PubMed1995

Insulinotropic action of human glicentin in dogs.

Glicentin has been demonstrated to be released in response to the intraluminal administration of nutrients, but its biological action remains unknown. To clarify the effect of glicentin on the endocrine function of the pancreas, the present study was performed using an in vivo local circulation system of the canine pancreas. During infusion of 0.5% solution of glucose or arginine, 100 and 400 pmol glicentin and 400 pmol glucagon were administered into the pancreaticoduodenal artery (PA) within 10 minutes at 40-minute intervals successively. During glucose infusion, blood glucose in the femoral artery did not change following administration of 100 pmol glicentin, but slightly increased following 400 pmol glicentin. Plasma insulin (immunoreactive insulin [IRI]) in the pancreaticoduodenal vein (PV) increased significantly only following infusion of 400 pmol glicentin. Plasma glucagon (immunoreactive glucagon [IRG]), measured with a specific antiserum to the C-terminal portion of glucagon, did not change following administration of 100 pmol glicentin, but was slightly elevated following 400 pmol glicentin. Plasma total IRG, measured with a nonspecific antiserum, increased promptly after administration of 100 and 400 pmol glicentin. During arginine infusion, the response of plasma IRI to glicentin was markedly exaggerated both in dosages of 100 and 400 pmol. From the present study it was concluded that human glicentin clearly increases insulin release from the canine pancreas.

Animals↗

PubMed1986

Effect of glicentin-related peptides on glucagon secretion in anaesthetized dogs.

Recent studies have demonstrated that glicentin is released during nutrient ingestion. However, the biological function of glicentin remains unclear. In order to clarify the role of glicentin in the enteroinsular axis, the effect of glicentin-related peptides was investigated using in vivo local circulation of canine pancreas. Peaks I and II of gut glucagon-like immunoreactivity, partially purified from porcine intestinal extract by affinity chromatography and gel filtration, synthesized hexadecapeptide of N-terminal glicentin (1-16) and synthesized octapeptide of C-terminal glicentin (62-69) were administered for 10 min into the pancreaticoduodenal artery of canine pancreas. Blood samples were then drawn from the pancreaticoduodenal vein. The administration of peak I of glucagon-like immunoreactivity during arginine infusion in a dosage of 20 ng reduced the glucagon secretion by 42 pmol/l (p less than 0.05), whereas peak II of glucagon-like immunoreactivity (20 ng) slightly increased the plasma level of insulin, although not significantly. The administration of glicentin (1-16) in a dosage of 400 ng during saline infusion did not alter the plasma insulin level, but reduced the plasma glucagon level in the pancreaticoduodenal vein by 29 pmol/l (p less than 0.05). In addition, glicentin [62-69] in a dosage of 400 ng exerted a decrease in both the plasma insulin (40 mU/l, p less than 0.05) and glucagon level (27 pmol/l, p less than 0.05). The present study demonstrates the suppression of pancreatic glucagon release during the infusion of peak I glucagon-like immunoreactivity and N- or C-terminal glicentin-related peptide. Therefore, it is suggested that glicentin released during nutrient intake might inhibit the secretion of glucagon.

Animals↗

PubMed1988

Effect of glicentin-related peptides upon the secretion of insulin and glucagon in the canine pancreas.

In order to clarify responses of the endocrine pancreas to glicentin, four glicentin-related peptides were investigated in a local circulation preparation of the canine pancreas. These peptides were administered in a dosage of 200 pmole for 10 min into the pancreaticoduodenal artery under the continuous infusion of 0.5% arginine solution. In a group of six dogs, the administration of glicentin-related pancreatic peptide (GRPP) and glicentin 1-16 resulted in an increase in plasma insulin (IRI) and a decrease in plasma glucagon (IRG). In the other group of six dogs, the administration of glicentin 62-69 induced an increase in plasma IRI and a decrease in plasma IRG. Following the successive infusion of oxyntomodulin, both plasma IRI and IRG increased slightly. Porcine glucagon administered at the end of each experiment exerted a rise in blood glucose and plasma IRI in addition to an increase in plasma IRG. In comparison of the maximal responses of plasma IRI and IRG to these glicentin-related peptides, the administration of glicentin 1-16, 62-69 or GRPP elicited an increase in plasma IRI and a decrease in plasma IRG. In contrast, oxyntomodulin and glucagon increased both plasma IRI and IRG. The present study indicates that glicentin-related peptides, both the N- and C-terminal portions, affect the endocrine function of the pancreas and suggests that glicentin released by nutrient ingestion plays an important role in the enteroinsular axis.

Animals↗

PubMed1981

Relationship of glicentin to proglucagon and glucagon in the porcine pancreas.

We have previously isolated from porcine small intestine a peptide known as glicentin. The C-terminal portion of glicentin consists of the sequence of glucagon extended at its C terminus by an octapeptide, and differs slightly from the sequence of a proposed fragment of proglucagon. Glicentin-like material has been demonstrated in the pancreatic A cell, wherein it is located in the periphery of the secretory granules, whereas glucagon is located in the centre of the granules. To study the relationship of glicentin to the biosynthesis of glucagon, we have now investigated the glucagon-like and glicentin-like peptides in extracts and perfusates of the porcine pancreas. Our findings that a peptide with glicentin-like immunoreactivity, and intermediate in size between glicentin and glucagon, is secreted synchronously with glucagon suggest that this glicentin-related peptide is a major cleavage product of proglucagon.

Animals↗

PubMed1997

Trophic effects of glicentin on rat small-intestinal mucosa in vivo and in vitro.

To define the role of glicentin the active site of enteroglucagon, we evaluated the trophic effects of recombinant rat glicentin on rat small intestine and IEC-6 cells. In vivo, a significant increase was observed in jejunal wet weight, protein content, DNA content, and alkaline phosphatase activity after the subcutaneous administration of 100 micrograms/kg per day of glicentin for 2 weeks. In the ileum, however, there were no significant differences between the control versus glicentin groups in any of these parameters. Ornithine decarboxylase (ODC) activity 3.5 h after an intraperitoneal injection of glicentin was increased in the jejunal mucosa, but not in the ileal mucosa. In vitro, glicentin, at a dose of more than 100 ng/ml, significantly increased both tritium-thymidine incorporation and the number of IEC-6 cells. These findings indicate that glicentin exerts direct trophic effects on the rat small-intestinal mucosa and on the rat small-intestinal cell line, IEC-6, and that this peptide appears to be an active site of enteroglucagon.

Alkaline Phosphatase↗

PubMed1980

Glucagon- and glicentin-immunoreactive cells in the human digestive tract.

The distribution and cellular location of substances reacting with anti-glucagon or anti-glicentin sera, i.e., glucagon-like and glicentin-like immunoreactivities, were studied in the human digestive tract using the immunofluorescence and immunoperoxidase methods. Both types of immunoreactivity were (1) absent in the antrum, (2) abundant in cells located at the periphery of pancreatic islets, (3) unevenly present in cells scattered in the epithelium of the small intestinal mucosa, the glicentin-immunoreactive cells being particularly abundant in the ileum. In the pancreas, and, when simultaneously present, in the intestine, both glucagon and glicentin immunoreactivities were located in the same cells. The precise ultrastructural location of each immunoreactivity was readily made using colloidal gold and ferritin tracers on ultrathin sections of glutaraldehyde-osmium fixed and epoxy resin-embedded tissues. In the pancreas, both glucagon and glicentin immunoreactivities were found in the granules of the A-type cells; the glucagon immunoreactivity was only present in the core of the granule, whereas the glicentin immunoreactivity was found either in the peripheral halo only, or throughout the entire granule. In the small intestine, both immunoreactivities were located inside the granules of the L-type cells. Quantitative specificity tests suggested that the glucagon- and the glicentin-like substances of the pancreas differ from those found in the intestine.

Cytoplasmic Granules↗

PubMed1984

Immunohistochemical studies on glucagon, glicentin and pancreatic polypeptide in human stomach: normal and pathological conditions.

Endocrine-like cells containing glucagon, glicentin or pancreatic polypeptide immunoreactivity in human foetal and adult stomach, with or without disease, were studied with the indirect immunoperoxidase method and mirror sectioning technique. In foetal and neonatal oxyntic mucosae, there were endocrine-like cells with glucagon and glicentin immunoreactivities and argyrophilia. Cells containing glicentin immunoreactivity alone were detected earlier than glucagon cells during foetal development, and were also distributed throughout foetal to neonatal life. Bovine pancreatic polypeptide immunoreactivity coexisted in a subpopulation of the glucagon-glicentin cells. These cells were absent from normal oxyntic mucosa in the postneonatal period and from normal antral mucosa throughout life. Hamartomatous polyp in adult oxyntic mucosa, hyperplastic oxyntic mucosa in Menetrier's disease and atrophic oxyntic mucosa in a remnant stomach with cancer showed scattered glucagon-glicentin cells, but few or no cells containing bovine pancreatic polypeptide. Intestinalized mucosa showed plentiful glicentin cells with occasional glucagon and/or bovine pancreatic polypeptide immunoreactivity. Some gastric cancer cells of both diffuse and adenoplastic types contained immunoreactive glicentin and, less frequently, glucagon. Bovine pancreatic polypeptide immunoreactivity was detected in a few adenoplastic cancer cells, but not in diffuse type cells. Three different anti-pancreatic polypeptide sera against bovine, porcine or human pancreatic polypeptide detected basically the same cells mentioned above, but pancreatic polypeptide cells lacking human pancreatic polypeptide immunoreactivity were also present in foetal oxyntic mucosa. Immunoabsorption tests revealed that the bovine pancreatic polypeptide immunoreactivity was remote from peptide YY and neuropeptide Y.

Adolescent↗

PubMedDate not supplied

Response of plasma glicentin to intraduodenal administration of glucose in piglets.

Controversial results concerning the secretion of glicentin prompted us to investigate the response of circulating glicentin to intraduodenal administration of glucose in piglets. A 20% solution of glucose (2 g/kg) was administered into the duodenum of six piglets in a fully conscious state. As blood glucose rose, plasma insulin increased to a peak of 21 +/- 4 microU/ml. Plasma glucagon, determined by C-terminal-specific antiserum, was 70 +/- 30 pg/ml at fasting and slightly increased after the glucose load. Plasma immunoreactive glucagon measured by cross-reacting glucagon antiserum increased from the baseline of 1563 +/- 260 to a peak of 4738 +/- 415 pg/ml at 120 min. Plasma glicentin determined by antiserum R 64 was 463 +/- 81 pmol/l at baseline and reached a peak level of 1081 +/- 174 pmol/l at 90 min. The percent changes of plasma glucagon from the fasting level measured by cross-reacting antiserum and glicentin were 296 and 233%, respectively. There was a significant correlation between plasma glucagon measured by cross-reacting antiserum and glicentin (r = 0.817, P less than 0.001). Chromatography of plasma obtained during glucose load revealed the heterogeneity of glicentin. It can be concluded from the present study that glicentin is clearly secreted in response to intraluminal administration of glucose.

Animals↗

PubMedDate not supplied

Response of plasma glicentin to fat ingestion in piglets.

In order to elucidate the response of plasma glicentin to fat ingestion, butter, glycerol or palmitate was administered into the duodenum of piglets in a fully conscious state and plasma glicentin and glucagon were determined. Butter instillation did not change blood glucose. Plasma triglyceride rose gradually 120 min after butter loading. Plasma insulin and glucagon measured by antiserum specific to the C-terminal slightly increased following butter administration and plasma total glucagon and glicentin increased gradually and significantly. The increments of total glucagon and glicentin were 179 and 158%, respectively. However, chromatography of porcine plasma obtained during fat loading revealed heterogeneity of glicentin-related peptides. Glycerol ingestion induced a slight rise of plasma total glucagon. Administration of palmitate revealed an increase in plasma total glucagon and glicentin. The present study clearly demonstrates the secretion of glicentin following fat ingestion, which might be caused by the hydrolysates of triglyceride, as suggested in previous dog experiments.

Animals↗

PubMed1986

Renal catabolism of 125I-glicentin.

The renal catabolism of 125I-glicentin has been studied in vivo by the disappearance of this peptide from the plasma of bilaterally nephrectomized, ureteral-ligated, or normal rats and by using tubular microinfusion techniques. In addition the catabolism of glicentin by the isolated, perfused kidney has been studied. Results from in vivo studies demonstrated that half-disappearance time was lower in control (59.5 +/- 1.8 min) than in bilaterally nephrectomized rats (97.2 +/- 2.6 min), and this value was significantly higher than that of ureteral-ligated animals (83.2 +/- 1.1 min, P less than 0.005). Microinfusion experiments revealed that when 125I-glicentin was injected into the proximal tubule, no trichloroacetic-precipitable radioactivity was recovered in the urine, whereas most of inulin injected was recovered. By contrast most of the 125I-glicentin injected into the distal tubule was recovered in the urine. In isolated kidney experiments, organ clearance rate of 125I-glicentin averaged 0.88 +/- 0.10 ml/min, a value significantly higher than that of glomerular filtration rate (0.72 +/- 0.06 ml/min, P less than 0.005, paired data), and both parameters showed a close linear relationship (r = 0.90). Urinary clearance of glicentin was negligible. These results demonstrate that the kidney plays a major role in the catabolism of glicentin, mainly by glomerular filtration and tubular catabolism. The site of tubular catabolism appears to be the proximal tubule. Peritubular uptake was minimal.

Animals↗

PubMed1979

Glicentin immunoreactive cells: their relationship to glucagon-producing cells.

The cellular and subcellular localization of one of the gut glucagon-like immunoreactants (GLI-1 or glicentin) and the relative distribution of glicentin- and glucagon-containing cells were investigated by immunocytochemistry. By immunofluorescence, the antiglicentin serum, which does not react with glucagon, revealed positive cells in the islets of Langerhans and in the gut mucosa, particularly in the terminal ileum and colon. In the intestinal mucosa, it was proven ultrastructurally that the glicentin immunoreactive cells correspond to the L cell and that the secretory granules represent the storage compartment of the immunoreactive material. In pancreatic islets, consecutive semithin sections treated with antiglicentin and specific antiglucagon sera showed that the same A cell population reacted with both sera, while immunoperoxidase staining on thin sections revealed that the immunoreactive material was confined to the secretory granules. The same results were obtained on dog oxyntic mucosa, where the glicentin- and glucagon-containing cells were identified as the gastric A cell. The immunocytochemical demonstration of a common glicentin-like material in the A and L cells together with the known presence of a common immunoreactant in glicentin and glucagon strongly support the idea that the A and L cells are ontogenetically related and synthesize their secretory product via a glicentin-like precursor which, by specific cleavage, could yield glucagon and gut glucagon-like immunoreactants.

Animals↗

PubMed1981

The amino acid sequence of porcine glicentin.

Glicentin or gut GLI-1 has previously been isolated from porcine small intestine. On the basis of the available chemical data, the molecule was thought to contain 100 amino acid residues. A redetermination of the amino acid composition of the molecule has shown it to contain 69 amino acid residues, and the full sequence has been established. The sequence of glicentin can be outlined as: GRPP1--30-Lys-Arg-Glucagon33--61-Lys-Arg-Hexapeptide64--69 where GRPP1--30 probably corresponds to the glicentin related pancreatic peptide previously isolated from porcine pancreas. In the pancreas, the two dibasic sequences (Lys31-Arg32 and Lys62-Arg63) probably represent sites of post-synthetic enzymatic cleavages by analogy with the two dibasic sequences of proinsulin. Glicentin thus fulfills the structural requirements for being all or a part of porcine proglucagon. In the intestine, glicentin could be the precursor of oxyntomodulin, a small molecular weight gut GLI presumably identical to glicentin 33--69, i.e., glucagon extended at the C-terminal end by an octapeptide.

Amino Acid Sequence↗

PubMed1980

Glicentin and gastric inhibitory polypeptide immunoreactivity in endocrine cells of the gut and pancreas.

The distribution of the postulated glucagon precursor, glicentin, as well as of the gastrointestinal hormone GIP (gastric inhibitory polypeptide), has been studied by immunocytochemistry and radioimmunoassay. Our results show that GIP antisera may contain a population of antibodies recognizing an immunoreactant common to glicentin and GIP. The occurrence of such common immunoreactants makes immunological distinction between the two hormones difficult and may explain previous results indicating that GIP is stored by glucagon cells. The present results indicate that GIP is produced by endocrine cells of the duodenum and jejunem and is absent from the pancreas, stomach, and large intestine. Glicentin-like immunoreactivity is displayed by A cells of the pancreas and by oxyntic A cells of the stomach, as well as by numerous glucagon-like immunoreactant (GLI) cells of the ileum and colon. Use of glucagon ad glicentin antisera of differing specificities indicates that the processing of this putative prohormone differs between A cells and GLI cells. Studies on the ontogeny of pancreatic A cells also reveal differences in the reactivity pattern of glicentin-like immunoreactivity between fetal and adult rats. Ultraimmunocytochemical studies show that glicentin-like immunoreactivity is mainly, stored in the cytoplasmic granules of pancreatic A cells.

Aging↗

PubMed1988

Oxyntomodulin and glicentin: brain-gut peptides in the rat.

Glucagon-like materials and glucagon have been identified by immunoassay and immunocytochemistry in the mammalian central nervous system. However, the molecular forms relevant to brain glucagon-like immunoreactivity (GLI) have not been precisely defined. In the rat small intestine, more than 90% of GLI is constituted by two peptides: oxyntomodulin (OXM) and glicentin. This work was initiated to characterize and determine the concentrations of these two peptides and glucagon in the rat central nervous system and to compare their relative proportions with those found in the gut. Different regions from the adult rat brain were analyzed by HPLC in association with RIA, using a central glucagon antiserum and an antibody directed toward the C-terminal end of OXM and glicentin. The elution profiles of hypothalamus extracts were constituted by two main peaks, both detected by the two antibodies used and displaying the same retention times as glicentin and OXM, respectively. A third small peak, which coeluted with glucagon, was constantly recorded with the central glucagon antiserum. The percentages of glicentin, OXM, and glucagon in 10 hypothalami were 37 +/- 1%, 55 +/- 1%, and 8 +/- 2%, respectively (n = 8). This distribution was quite similar to that in small intestinal extracts (38 +/- 1%, 59 +/- 1%, and 1.3 +/- 0.1%, respectively; n = 7); however, the peptide concentrations were almost 50-fold greater in intestine than in hypothalamus. In the medulla oblongata, the same peptide ratio was observed, with 10-fold lower concentrations compared to those in hypothalamus. In olfactory bulb, cerebellum, and cortex the concentrations were close the the detection limit, whereas they could be not detected in the pituitary. The combination of HPLC and specific RIAs allowed us to unambiguously characterize OXM and glicentin as the major components of GLI in the rat hypothalamus and medulla oblongata. The same proportion of these two peptides in the central nervous system and the gut indicates that a similar posttranslational processing exists in these rat tissues, another example of the brain-gut axis.

Animals↗

PubMed1997

Helicobacter pylori infection accelerates gene expression of glicentin in the gastric mucosa. Its association with intestinal metaplasia of the stomach.

BACKGROUND: Glicentin is an intestinal polypeptide hormone which seems to promote intestinal metaplasia (IM) in the gastric mucosa. The aim of this study was to clarify whether Helicobacter pylori infection accelerates glicentin gene expression. METHOD: Glicentin mRNA was investigated by reverse-transcription polymerase chain reaction using gastric biopsies from 47 patients examined endoscopically and denying IM. RESULTS: IM was observed in 18 (38.3%) cases histologically, but not in the other 29 (62.7%). Glicentin mRNA was significantly correlated with histological IM (P < 0.01) and was positively correlated with H. pylori infection (P < 0.05). CONCLUSION: Our results indicate that H. pylori infection is associated with the induction of glicentin in the gastric mucosa, thus supporting the hypothesis that H. pylori infection accelerates IM of the stomach.

Adult↗

PubMed1988

Distribution of glucagonlike peptide I (GLP-I), glucagon, and glicentin in the rat brain: an immunocytochemical study.

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.

Animals↗

PubMed1986

Glicentin 1-61 probably represents a major fraction of glucagon-related peptides in plasma of anaesthetized uraemic pigs.

Uraemia was induced in pigs by ligation of the renal vascular pedicle, and uraemic plasma was analysed for glucagon and glucagon-related peptides. A preponderance of large molecular weight (Mr) components comprising glicentin and moieties of slightly lower Mr was found, accounting for 73 +/- 3% (mean +/- SEM, n = 12) of the total plasma glucagon-like immunoreactivity. Comparisons with glicentin 1-61, produced by controlled, stepwise, consecutive digestion of purified natural glicentin with carboxypeptidases (carboxypeptidase A followed by carboxypeptidase B, and again by carboxypeptidase A and B), gel filtration, ion exchange chromatography, reverse phase HPLC and radioimmunoassays for the glucagon sequences 6-15 and 19-29 and for the glicentin sequence 12-30 all indicate that glicentin 1-61 constitutes approximately 57% of the large Mr glucagon-related peptides found in uraemia in pigs.

Amino Acid Sequence↗