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Biomedical subjects

D Bataille

Publications and source records attributed to D Bataille.

At least 91 records · Page 5Linked to original sources
PubMed1986

Solid-phase peptide synthesis of human(Nle-27)-oxyntomodulin. Preliminary evaluation of its biological activities.

Oxyntomodulin is a peptide isolated from porcine intestine which consists of the whole glucagon sequence extended at its C-terminal part by a basic octapeptide. The analogue (Nle-27)-oxyntomodulin of the human sequence has been synthesized by solid-phase peptide synthesis, purified by HPLC and identified. Its biological activities are the same as those of the natural hormone.

Amino Acid Sequence↗
PubMed1986

The biological significance of "enteroglucagon." Present status.

"Enteroglucagon" refers to glucagon-like peptides present in intestine that cross react with N-terminally directed antiglucagon antisera but not with C-terminally directed antisera. Two peptides having these features have been isolated from the lower small intestine: glicentin (69 amino acids) and oxyntomodulin (37 amino acids). The sequence of the pancreatic preproglucagon gene suggests that glucagon, glicentin and oxyntomodulin derive from the same translational pathway, each individual peptide being produced by different posttranslational processing. Both glicentin and oxyntomodulin contain the glucagon sequence that bears the N-terminal epitope and are C-terminally extended by the same octapeptide masking the C-terminal epitope. The N-terminal 32 amino acid extension of glicentin renders the molecule unable to bind to hepatic glucagon receptors, unlike glucagon and oxyntomodulin. An original tissue specificity of oxyntomodulin, mediated by a novel type of receptor, has been observed in acid secreting gastric oxyntic glands. Oxyntomodulin and glicentin containing the C-terminal octapeptide, as well as the octapeptide itself, are able to inhibit gastric acid secretion. This biological activity is likely to represent the main physiological regulatory pattern in which "Enteroglucagon" is involved.

Animals↗
PubMed1986

Functional receptors for VIP, GIP, glucagon-29 and -37 in the HGT-1 human gastric cancer cell line.

Three separate sets of receptors sensitive to VIP, GIP and pancreatic/entero-glucagons, have been characterized in HGT-1 cells. The order of relative potencies of VIP receptor agonists was VIP greater than rh GRF-43, rh GRF-29 greater than PHI greater than hp GRF-40, secretin. G-37 was about 4 times less potent than G-29 in HGT-1 cells (G-29 greater than G-37), whereas it was about 20 times more potent than G-29 in rat fundic glands (G-37 greater than G-29). Adenylate cyclase in HGT-1 cells was stimulated by VIP, G-29, G-37 and GIP, over a concentration from 3.16 X 10(-9) to 3.16 X 10(-7) M GIP. The experimental data: (1) support the enterogastrone activity of GIP, via adenylate cyclase activation and somatostatin release by gastric D cells; (2) demonstrate that HGT-1 cells originating from a human fundic tumor are sensitive to the glucagon-like peptides G-29 and -37, as rat fundic glands; (3) indicate that the pharmacological properties of the VIP receptor in this human gastric cell line are similar to those characterized in normal human gastric glands.

Adenylyl Cyclases↗
PubMed1986

Secretin receptor activity in rat gastric glands. Binding studies, cAMP generation and pharmacology.

We measured 125I-secretin binding to membranes prepared from rat fundic glands and compared the abilities of natural and synthetic secretin (SN) analogs to inhibit 125I-secretin binding and to activate the cAMP generating system in glandular and subcellular preparations from the fundus and antrum. The natural peptides structurally related to porcine secretin (pSN) included: chicken secretin (cSN), vasoactive intestinal peptide (VIP), porcine peptide with N-terminal histidine and C-terminal isoleucine amide (PHI), helodermin, growth hormone releasing factors isolated from the rat hypothalamus (rhGRF-43, rhGRF-29) or from a human pancreatic tumour (hpGRF-40). These peptides inhibited the binding of 125I-secretin to rat fundic membranes: pSN greater than cSN greater than PHI, VIP and activated the cAMP generating system in fundic glands, according to the following order of potency; pSN greater than cSN greater than PHI, VIP greater than rhGRF-29 greater than rhGRF-43. Porcine peptide with N-terminal tyrosine and C-terminal tyrosine (PYY), GIP, SOM and hpGRF-40 were inactive. Structural requirements for secretin receptor activity were evaluated with four synthetic secretin analogs corresponding to porcine secretin substituted at the N-terminal end by sequence portion of VIP, GIP, GLU and SOM: Ala4-Val5-SN(VIP-SN); Tyr1-Ala2-Glu3-SN (GIP-SN); Gln3-SN (GLU-SN) and Phe1-Phe1-Trp3-Lys4-SN (SOM-SN). The relative potencies of the analogs in fundic and antral preparations were: pSN greater than VIP-SN greater than VIP, GIP-SN greater than GLU-SN greater than SOM-SN for 125I-secretin displacement and cAMP production (glandular cAMP generation and adenylate cyclase activation).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1986

Ectopic G-29 and G-37 glucagon secretion by hypercalcemic infantile renal tumors.

Four hypercalcemic infantile renal tumors were shown to secrete glucagon-like peptides. These unusual tumors were histologically classified as rhabdoid tumors of the kidney (3 cases) and a cellular mesoblastic nephroma (1 case). Elevated G-29 and G-37 glucagon levels were detected in the plasma and tumor extracts as well as in the supernatants of cultured tumor explants. Three of these tumors were heterotransplanted into the nude mice and serially passaged from a mouse to another. The glucagon level decreased in the transplanted tumor extracts with the number of passage.

Animals↗
PubMed1986

Oxyntomodulin and its C-terminal octapeptide inhibit liquid meal-stimulated acid secretion.

Oxyntomodulin (OXM), a 37-amino acid glucagon-containing peptide produced mainly in intestine and endocrine pancreas, is present in rat plasma and inhibits pentagastrin-stimulated gastric acid secretion in both the anesthetized and the conscious rat. In order to investigate the modifications in acid and water secretions in a physiological model, we set up a protocol which allowed us to study acid secretion in the conscious rat both under basal conditions (during an 18-hour fast) or after a physiological stimulus (a liquid meal). OXM (110 pmol X kg-1) did not modify the basal acid or water output in an 18-hour fasting state. When injected before the test meal, OXM (225 pmol X kg-1) sharply decreased the acid output stimulated by a liquid meal (milk), which represented 10 times the basal value. Results are compared to those obtained when pentagastrin was the stimulant. Synthetic C-terminal octapeptide of OXM was able to inhibit both basal and meal-stimulated secretions. We can conclude that OXM, or a closely related peptide containing the C-terminal octapeptide, may be a physiological regulator of gastric functions.

Animals↗
PubMed1986

Somatostatin enhances the inhibitory effect of oxyntomodulin and its C-terminal octapeptide on acid secretion.

Somatostatin (SOM) and oxyntomodulin (OXM) are two natural peptides present in the gut which display inhibitory effects on gastric acid secretion in rat. Possible interactions between the effects of these two molecules were tested in the anesthetized rat, using as the stimulant either pentagastrin or histamine at doses that induced 30% of the maximal responses. SOM was tested at sub-threshold doses and OXM at doses inducing an inhibition of less than 50%. SOM induced a highly significant potentiation of the action of OXM both on pentagastrin- and histamine-induced secretion. Similarly, SOM enhanced the inhibitory effects of the C-terminal octapeptide of OXM. Whatever the mechanism involved, this potentiating effect of SOM might be of importance in the in vivo biological effect of OXM.

Animals↗
PubMed1985

Oxyntomodulin (glucagon-37) and its C-terminal octapeptide inhibit gastric acid secretion.

Oxyntomodulin (OXM) is a peptide isolated from porcine intestine which consists of the whole glucagon sequence with a basic octapeptide (KA8) at its C-terminal end. In this study, the effect of OXM and KA8 on pentagastrin-stimulated gastric acid secretion has been studied in conscious rats and cats. In rats, OXM (25-450 pmol . kg-1) as well as KA8 (7.5-60 nmol . kg-1) inhibited pentagastrin-stimulated gastric acid output in a dose-dependent manner; KA8 was about 100-times less potent than OXM. In cats, KA8 (90 nmol . kg-1) was also an inhibitor of acid secretion. We conclude that OXM, or a closely related peptide, could be a physiological modulator of gastric acid secretion, and that the C-terminal octapeptide of OXM is implicated in this effect.

Animals↗
PubMed1985

Synthesis of the C-terminal octapeptide of pig oxyntomodulin. Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala: a potent inhibitor of pentagastrin-induced acid secretion.

The synthesis of Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala representing the C-terminal octapeptide of oxyntomodulin isolated from pig intestine is described. Its structure was confirmed by its 360-MHz 1H NMR spectra. The octapeptide was tested for its ability to inhibit pentagastrin-induced acid secretion, in the anaesthetized rat, in the conscious rat with chronic gastric fistula, and in the conscious cat with gastric chronic fistula. The octapeptide inhibits pentagastrin-induced acid secretion in all three models. Compared to oxyntomodulin, the parent hormone, the synthetic peptide was approximately 150 times less potent but has the same efficacy. Biological data are presented and discussed.

Animals↗
PubMed1984

A pure enteroglucagon, oxyntomodulin (glucagon 37), stimulates insulin release in perfused rat pancreas.

Oxyntomodulin, a gut peptide recently purified, has been tested in isolated perfused pancreases of normal rats. It was shown to stimulate insulin release monophasically in the presence of a low (6 mM) glucose concentration in the medium. Furthermore, oxyntomodulin potentiated glucose-induced insulin release (10 mM glucose) in a dose-dependent manner, although it was less powerful in this respect than equimolar concentrations of pancreatic glucagon. As oxyntomodulin belongs to the gut glucagon-like immunoreactants which are released during digestion, it is suggested that oxyntomodulin might be one of the factors that could functionally link the gut and the endocrine pancreas and contribute, at least in part, to the regulation of postprandial insulin release.

Animals↗
PubMed1984

[Demonstration of a specific receptor site for glucagon-37 (oxyntomodulin/bioactive enteroglucagon) in rat oxyntic glands].

In this work, we show directly the existence of specific binding sites for Glucagon-37 (G-37) in isolated oxyntic glands from rat fundic mucosa. The binding of 125I-Glucagon-37 was inhibited by G-37 with a dissociation constant KD = 2.6 X 10(-9) M (high affinity binding capacity = 85 fmol/mg of protein) and by pancreatic Glucagon (G-29) with a KD = 2.2 X 10(-8) M. These results confirm the tissue specificity of G-37, evidenced in vitro on the cyclic AMP production by the same glands and in vivo on the inhibition of gastric acid secretion. They suggest that these activities are related to the G-37-binding on this novel receptor site for Glucagon-related peptides, which is distinct from receptors for the main stimulants of acid secretion, such as Gastrin, Histamine or cholinergic agents.

Animals↗
PubMed1982

Isolation of glucagon-37 (bioactive enteroglucagon/oxyntomodulin) from porcine jejuno-ileum. Isolation of the peptide.

A 37 amino acid-peptide has been isolated from porcine jejuno-ileum on the basis of its glucagon-like activity in liver (interaction with glucagon-binding sites and activation of adenylate cyclase) using gel filtration, ion-exchange and high-performance liquid chromatography. Depending on the criteria chosen, this peptide is referred to as either 'bioactive enteroglucagon' (activity in liver), 'oxyntomodulin' (specific action in gastric oxyntic glands) or 'glucagon-37' (chemical structure).

Adenylyl Cyclases↗
PubMed1982

Isolation of glucagon-37 (bioactive enteroglucagon/oxyntomodulin) from porcine jejuno-ileum. Characterization of the peptide.

A peptide isolated from porcine gut according to its glucagon-like activity in liver (bioactive enteroglucagon) has been characterized immunologically, biologically and chemically: its potency relative to pancreatic glucagon in interacting with an antiglucagon antibody, hepatic glucagon-binding sites and hepatic adenylate cyclase was approximately 100%, 20% and 10%, respectively. In contrast, it is approximately 20-times more potent than glucagon in oxyntic glands, justifying the term 'oxyntomodulin'. Chemically, it consists in the 29 amino acid-peptide glucagon elongated at its C-terminal end by the octapeptide Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala; accordingly, it is called 'glucagon-37'.

Amino Acid Sequence↗
PubMed1982

The interaction of glucagon, gastric inhibitory peptide and somatostatin with cyclic AMP production systems present in rat gastric glands.

The effects of glucagon, gastric inhibitory peptide (GIP) and somatostatin on the generation of cyclic AMP have been studied under basal and histamine- or secretin-stimulated conditions in tubular gastric glands isolated by means of EDTA from the rat fundus and antrum. Four types of cell could be identified by electron microscopy; namely, parietal, mucous, peptic and some endocrine cells with a good morphological preservation of the cellular topography as seen in the intact mucosa. Immunoreactive somatostatin was found in antral glands (210 +/- 16 ng/g cell, wet wt., n = 9) as well as in fundic glands, but in smaller concentration (50 +/- 8 ng/g cell, wet wt., n = 9). (1) In rat fundic glands, glucagon, in supraphysiologic doses (3 . 10(-9) -5 . 10(-7) M), raised cyclic AMP levels 46 times above the basal. At maximally effective doses, combination of glucagon plus histamine was not additive whereas glucagon and secretin stimulations resulted in an additive response. Somatostatin (10(-10) -10(-7) M) inhibited both glucagon- and histamine-induced cyclic AMP production, whereas cimetidine specifically blocked the histaminergic stimulation. (2) In the same conditions, 10(-6)M glucagon produced a marginal effect (4-fold increase) in rat antrum, whereas GIP (10(-9) -10(-6)M) was unable to induce a significant rise of cyclic AMP production in either fundic or antral glands, or to prevent cyclic AMP production stimulated by histamine. (3) The present data do not support the view that circulating glucagon or GIP may regulate gastric secretion directly by a cyclic AMP-dependent mechanism in rat gastric glands and raise the possibility that gastric somatostatin may be the final mediator of the inhibitory actions of these hormones on acid secretion. (4) It is proposed that pancreatic glucagon acts through a receptor-cyclic AMP system which is specific for the bioactive peptide enteroglucagon ('oxyntomodulin'), probably in rat parietal cells.

1-Methyl-3-isobutylxanthine↗
PubMed1981

[Bioactive "enteroglucagon" (oxyntomodulin): evidence for a C-terminal extension of the glucagon molecule].

The bioactive fraction of "enteroglucagon" has been isolated from the porcine jejuno-ileum on the basis of its glucagon-like action in liver. High performance liquid chromatography analysis followed by Dansylation of peptide fragments obtained after enzymatic digestion of both this peptide and glucagon suggests that the bioactive "enteroglucagon" contains the glucagon molecule plus a C-terminal extension under the from of the octapeptide. Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala-COOH. The presence in the native molecular of a structural difference of modification as compared to glucagon in the 1-11 fragment is possible.

Amino Acid Sequence↗
PubMed1981

[Effect of vasoactive intestinal peptide (VIP) on prolactin secretion in man].

The effect of Vasoactive Intestinal Peptide (VIP) on plasma prolactin has been tested in two human subjects. When perfused at low doses (few micrograms per minute), VIP increased the prolactin levels in both sexes, the response being more important in Woman (3.5-fold over basal) than in Man (2-fold). VIP may be a physiological regulator of prolactin release in humans. This peptide may be a specific tool for the clinical investigation of the prolactin function.

Adult↗