Effect of glicentin, oxyntomodulin and related peptides on isolated gastric smooth muscle cells

Rodier, Geneviève; Magous, Richard; Mochizuki, Tohru; Martinez, Jean; Nguyen, Duy Linh; Bali, Jean Pierre; Bataille, D.; Jarrousse, C.

doi:10.1007/s004240050458

Cited by 21 publications

(20 citation statements)

References 35 publications

(130 reference statements)

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“…A direct effect of GLP‐1 on gastric smooth muscle cells seems unlikely since the peptide changes neither the basal tone of gastric smooth muscle strips nor the length of smooth muscle cells 31,32 . Furthermore, studies in animals demonstrated that GLP‐1‐mediated effects on gastric emptying are dependent on an intact vagus nerve 15,16 .…”

Section: Discussionmentioning

confidence: 99%

GLP‐1 regulates gastroduodenal motility involving cholinergic pathways

Schirra

Nicolaus

Woerle

et al. 2009

Neurogastroenterology Motil

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The gut-born incretin hormone glucagon-like peptide-1 (GLP-1) delays gastric emptying. To elucidate the mechanisms by which GLP-1 affects gastroduodenal motility and glycaemia, we studied the effects of exendin(9-39), a potent GLP-1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double-blind, placebo-controlled, four-arm, cross-over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9-39), atropine, exendin(9-39) + atropine or saline were infused intravenously. Antro-pyloro-duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9-39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9-39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9-39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9-39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9-39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP-1 secretion. Cholinergic mechanisms mediate the effects of GLP-1 on postprandial gastric accommodation but not on antro-pyloro-duodenal motility. GLP-1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion.

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Section: Discussionmentioning

confidence: 99%

GLP‐1 regulates gastroduodenal motility involving cholinergic pathways

Schirra

Nicolaus

Woerle

et al. 2009

Neurogastroenterology Motil

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“…Thus, OXM most likely triggered insulin secretion by simultaneous activation of GLP-1 and glucagon receptors on ␤-cells (17). However, interaction with (an)other receptor(s) cannot be excluded, because OXM was shown (38) to induce contraction of antral smooth muscle cells in an in vitro model in which GLP-1 and glucagon had no effect at all.…”

Section: Discussionmentioning

confidence: 99%

Oxyntomodulin ameliorates glucose intolerance in mice fed a high-fat diet

Parlevliet¹,

Heijboer²,

Elst³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Parlevliet ET, Heijboer AC, Schröder-van der Elst JP, Havekes LM, Romijn JA, Pijl H, Corssmit EP. Oxyntomodulin ameliorates glucose intolerance in mice fed a high-fat diet. Am J Physiol Endocrinol Metab 294: E142-E147, 2008. First published October 30, 2007 doi:10.1152/ajpendo.00576.2007.-We evaluated the acute effects of OXM on glucose metabolism in diet-induced insulin-resistant male C57Bl/6 mice. To determine the effects on glucose tolerance, mice were intraperitoneally injected with OXM (0.75, 2.5, or 7.5 nmol) or vehicle prior to an ip glucose tolerance test. OXM (0.75 nmol/h) or vehicle was infused during a hyperinsulinemic euglycemic clamp to quantify insulin action on glucose production and disposal. OXM dose-dependently improved glucose tolerance as estimated by AUC for glucose (OXM: 7.5 nmol, 1,564 Ϯ 460, P Ͻ 0.01; 2.5 nmol, 1,828 Ϯ 684, P Ͻ 0.01; 0.75 nmol, 2,322 Ϯ 303, P Ͻ 0.05; control: 2,790 Ϯ 222 mmol ⅐ l Ϫ1 ⅐ 120 min). Insulin levels in response to glucose administration were higher in 7.5 nmol OXM-treated animals compared with controls. In basal clamp conditions, OXM increased EGP (82.2 Ϯ 14.7 vs. 39.9 Ϯ 5.7 mol ⅐ min Ϫ1 ⅐ kg Ϫ1 , P Ͻ 0.001). During insulin infusion, insulin levels were twice as high in OXMtreated mice compared with controls (10.6 Ϯ 2.8 vs. 4.4 Ϯ 2.2 ng/ml, P Ͻ 0.01). Consequently, glucose infusion rate (118.6 Ϯ 30.8 vs. 38.8 Ϯ 26.4 l/h, P Ͻ 0.001) and glucose disposal (88.1 Ϯ 13.0 vs. 45.2 Ϯ 6.9 mol ⅐ min Ϫ1 ⅐ kg Ϫ1 , P Ͻ 0.001) were enhanced in mice that received OXM. In addition, glucose production was more suppressed during OXM infusion (35.7 Ϯ 15.5 vs. 15.8 Ϯ 11.4% inhibition, P Ͻ 0.05). However, if these data were expressed per unit concentration of circulating insulin, OXM did not affect insulin action on glucose disposal and production. These results indicate that OXM beneficially affects glucose metabolism in diet-induced insulin-resistant C57Bl/6 mice. It ameliorates glucose intolerance, most likely because it elevates glucose-induced plasma insulin concentrations. OXM does not appear to impact on insulin action. animal model; gut hormone; glucose tolerance; insulin; hyperinsulinemic euglycemic clamp POSTTRANSLATIONAL PROCESSING OF PROGLUCAGON in the intestine and the central nervous system yields glucagon-like peptide-1 (GLP-1), GLP-2, glicentin, and oxyntomodulin (OXM) (18,32,35). OXM contains 37 amino acids, including the complete glucagon sequence with a basic octapeptide carboxyterminal extension (6). OXM is released from intestinal L cells into the blood in response to food ingestion in amounts proportional to caloric content (20,30). It potently inhibits meal-stimulated gastric acid and enzyme secretion in rodents and man (19).OXM appears to be an effective regulator of appetite and body weight. Intravenous infusion of OXM suppresses appetite and reduces food intake in humans during a buffet meal (14). Furthermore, both intracerebroventricular and intraperitoneal administration of OXM reduce food intake and body weight gain during refeeding in fasted rats (15,1...

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“…Oxyntomodulin was provided by Sigma (St Quentin Fallavier, France). Its biological activity tested in vitro 15 fully fitted with that obtained with natural OXM 23 . The C‐terminal fragment GLIC 51‐69 was produced using a solid‐phase synthesis procedure: its biological activity has been established 15 …”

Section: Peptidesmentioning

confidence: 74%

“…In vivo , GLIC 51‐69 has been shown to be as potent as OXM to inhibit gut secretions 7,13 . In vitro , the GLIC 51‐69 is 15 time less potent than GLIC on one target cell, which is the antral smooth muscle cell 15 . Thus, the fragment preferentially mimics the OXM effects, presumably on the vagus nerve 7 and the enteric nervous system 6 as demonstrated in rats.…”

Section: Discussionmentioning

confidence: 99%

Oxyntomodulin and glicentin are potent inhibitors of the fed motility pattern in small intestine

Pellissier

Sasaki²,

Le‐Nguyen

et al. 2004

Neurogastroenterology Motil

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Glicentin (GLIC) and oxyntomodulin (OXM or GLIC 33-69) are gut hormones which regulate digestion. They are known to reduce digestive secretions and to delay gastric emptying. Their biological activities on intestinal motility are still unknown. The effect of a systemic GLIC or OXM increase was investigated in rats on the food intake, the postprandial myoelectrical activity of small intestine and the orocaecal transit. An OXM or GLIC i.v. infusion was applied during the 5 min preceding food onset and during the first 15 min of food intake. This determined a three- to fourfold increase of the preprandial OXM-GLIC level. The OXM or GLIC plasma increase did not modify food intake. OXM infusion slowed down gastric emptying when the stomach contained 3/4 of the ingested food (before T 3 h). The quantity of food delivered in jejunum was subsequently smaller (P < 0.05). In the small intestine, the duration of postprandial myoelectrical activity (50-60 min g(-1) of ingested food) was reduced by 70% (P < 0.001) on duodenum or jejunum and by 54% (P < 0.01) on ileum in OXM-treated rats. An interdigestive motility profile was settled and an acceleration of both gastric emptying and transit rate was thereafter evidenced (after T 3 h). GLIC also reduced the duration of the postprandial myoelectrical activity on duodenum and jejunum (65 and 63% respectively, P < 0.05), but was not as efficient as OXM on ileum. In pathological states such as acute adult gastroenteritis, OXM and GLIC exhibit a two- to fivefold increase in their plasma concentrations. The present findings suggest that OXM and GLIC could, in that disease, contribute to exclude pathogens, due to their joined action on gut motility.

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Effect of glicentin, oxyntomodulin and related peptides on isolated gastric smooth muscle cells

Cited by 21 publications

References 35 publications

GLP‐1 regulates gastroduodenal motility involving cholinergic pathways

GLP‐1 regulates gastroduodenal motility involving cholinergic pathways

Oxyntomodulin ameliorates glucose intolerance in mice fed a high-fat diet

Oxyntomodulin and glicentin are potent inhibitors of the fed motility pattern in small intestine

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