Effect of liraglutide on intragastric pressure (IGP) and satiation during intragastric nutrient drink infusion in healthy volunteers

Does GLP-2 receptor expression change dynamically in fed and fasted states?

GLUCAGON-LIKE PEPTIDE-1 MODULATES EXCITATORY CHOLINERGIC NEUROTRANSMISSION OF MOUSE DUODENUM AND COLON

The incretin Glucagon-like-peptide-1 (GLP-1) is produced by enterendocrine L cells of the small intestine. It delays gastric emptying and reduces intestinal transit by inhibiting vagal activity. To date, no evidences are available about a direct peripheral influence on gastrointestinal smooth muscle cells. The purpose of the present study was to investigate in vitro the effects of GLP-1 on the spontaneous and evoked mechanical activity of murine duodenum and colon, recording intraluminal pressure, index of the circular mechanical activity, and isometric tension, index of the longitudinal mechanical activity. In both intestinal segments GLP-1 (up to 1 μM) did not affect spontaneous mechanica…

Gastric relaxation induced by glucagon-like peptide-2 and receptorial expression in fasted or high-fat diet fed mice.

GLP-2 receptor expression in excitatory and inhibitory enteric neurons and its role in mouse duodenum contractility

Background  Glucagon-like peptide 2 (GLP-2), a nutrient-responsive hormone, exerts various actions in the gastrointestinal tract that are mediated by a G-protein coupled receptor called GLP-2R. A little information is available on GLP-2R expression in enteric neurons and nothing on the interstitial cells of Cajal (ICC). Methods  We investigated presence and distribution of the GLP-2R in the mouse duodenum by immunohistochemistry and the potential motor effects of GLP-2 on the spontaneous and neurally evoked mechanical activity. Key Results  The GLP-2R was expressed by the myenteric and submucosal neurons. Labelling was also present in nerve varicosities within the circular muscular layer an…

Review article: a comparison of glucagon-like peptides 1 and 2.

Summary Background Recent advancements in understanding the roles and functions of glucagon-like peptide 1 (GLP-1) and 2 (GLP-2) have provided a basis for targeting these peptides in therapeutic strategies. Aim To summarise the preclinical and clinical research supporting the discovery of new therapeutic molecules targeting GLP-1 and GLP-2. Methods This review is based on a comprehensive PubMed search, representing literature published during the past 30 years related to GLP-1 and GLP-2. Results Although produced and secreted together primarily from L cells of the intestine in response to ingestion of nutrients, GLP-1 and GLP-2 exhibit distinctive biological functions that are governed by t…

Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors

Background  Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the enteroendocrine-L cells of small and large intestine and released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory effects on gastrointestinal motility through vagal afferents and central nervous mechanisms; however, no data is available about a direct influence on the gastrointestinal wall. Our aim was to investigate the effects of GLP-1 on the spontaneous and evoked mechanical activity of mouse duodenum and colon and to identify the presence and distribution of GLP-1 receptors (GLP-1R) in the muscle coat. Methods  Organ bath recording technique and immunohistochemistry wer…

Inhibition of the mechanical activity of mouse ileum by cactus pear (Opuntia Ficus Indica, L, Mill.) fruit extract and its pigment indicaxanthin.

We investigated, using an organ bath technique, the effects of a hydrophilic extract from Opuntia ficus indica fruit pulp (cactus fruit extract, CFE) on the motility of mouse ileum, and researched the extract component(s) responsible for the observed responses. CFE (10-320 mg of fresh fruit pulp equivalents/mL of organ bath) reduced dose-dependently the spontaneous contractions. This effect was unaffected by tetrodotoxin, a neuronal blocker, N(omega)-nitro-l-arginine methyl ester, a nitric oxide synthase blocker, tetraethylammonium, a potassium channel blocker, or atropine, a muscarinic receptor antagonist. CFE also reduced the contractions evoked by carbachol, without affecting the contrac…

Flavonoid-induced gastric relaxation: structure-activity relationship and mechanism of action.

Gastric relaxation induced by glucagon-like peptide-2 in mice fed a high-fat diet or fasted.

Glucagon-like peptide-2 (GLP-2) is a nutrient-responsive gut hormone that increases the intestinal absorption. Exogenous GLP-2 also induces gastric fundus relaxation with possible implications for emptying rate or feeling of satiety. GLP-2 actions are mediated by GLP-2 receptor (GLP-2R), located on enteric neurons and myofibroblasts in murine gastrointestinal tract. Because it is not known whether changes in the endogenous GLP-2R levels occur in different nutritional states, we examined the GLP-2R gene and protein expression in gastric fundus from standard diet (STD)-fed, 12-h and 24-h fasted and re-fed, or high-fat diet (HFD)-fed mice and we analyzed the mechanical responses to exogenous G…

Gastric relaxation induced by apigenin and quercetin: Analysis of the mechanism of action

Abstract Aims Recently, flavonoids have been shown to cause murine gastric relaxation. In the present study we examined the mechanism of action underlying gastric relaxation induced by apigenin and quercetin in isolated mouse stomach. Main methods The mechanical activity from the whole stomach was detected as changes in the endoluminal pressure and the response to increasing concentrations of both flavonoids were tested before and after different pharmacological treatments. Key findings Apigenin and quercetin-induced a concentration-dependent gastric relaxation, apigenin being more potent than quercetin. The responses were unaffected by 2′5′dideoxyadenosine, an inhibitor of adenylate cyclas…

Functional evidence for different roles of GABAA and GABAB receptors in modulating mouse gastric tone

Abstract The aims of the present study were to investigate, using mouse whole stomach in vitro , the effects of γ-aminobutyric acid (GABA) and GABA receptor agonists on the spontaneous gastric tone, to examine the subtypes of GABA receptors involved in the responses and to determine the possible site(s) of action. GABA induced gastric relaxation, which was antagonized by the GABA A -receptor antagonist, bicuculline, potentiated by phaclofen, GABA B -receptor antagonist, but not affected by 1,2,5,6-Tetrahydropyridin-4-yl methylphosphinic acid hydrate (TPMPA), GABA C -receptor antagonist. Muscimol, GABA A -receptor agonist, mimicked GABA effects inducing relaxation, which was significantly re…

Effects of glucagon-like peptide 1 on intestinal mechanical activity in mouse

Gastric relaxation induced by flavonoids: analysis of the underlying mechanisms.

Evidence for region-specific effects of glucagone-like peptide-2 in mouse stomach

GLUCAGON-LIKE PEPTIDE-1: GASTROINTESTINAL MOTILITY AND FOOD INTAKE

Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action.

Recently, we have showed that indicaxanthin, the yellow betalain pigment abundant in the fruit of Opuntia ficus indica, has remarkable spasmolytic effects on the intestinal contractility in vitro. Thus, the purpose of the present study was to investigate the mechanism of action underlying the observed response. We used organ bath technique to record the mechanical activity of the mouse ileum longitudinal muscle and ELISA to measure the levels of cAMP. Indicaxanthin induced inhibitory effects on spontaneous mechanical activity, which were unaffected by indomethacin, a non-selective inhibitor of cycloxygenase; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor of nitric oxide-…

Glucagon-like peptide-2 relaxes mouse gastric fundus in vitro.

Role of cholinergic neurons in the motor effects of glucagon-like peptide-2 in mouse colon

Glucagon-like peptide-2 (GLP-2) reduces mouse gastric tone and small intestine transit, but its action on large intestine motility is still unknown. The purposes of the present study were 1) to examine the influence of GLP-2 on spontaneous mechanical activity and on neurally evoked responses, by recording intraluminal pressure from mouse isolated colonic segments; 2) to characterize GLP-2 mechanism of action; and 3) to determine the distribution of GLP-2 receptor (GLP-2R) in the mouse colonic muscle coat by immunohistochemistry. Exogenous GLP-2 (0.1–300 nM) induced a concentration-dependent reduction of the spontaneous mechanical activity, which was abolished by the desensitization of GLP-…

Relaxant effects of flavonoids on the mouse isolated stomach: structure-activity relationships.

Flavonoids are a large heterogeneous group of benzo-gamma-pyrone derivatives, which are abundantly present in our diet. In this study we investigated the effects of six flavonoids (apigenin, genistein, quercetin, rutin, naringenin and catechin) on the gastric tone in mouse isolated stomach. The mechanical activity was recorded as changes of intraluminal pressure. All flavonoids tested produced a concentration-dependent relaxation, which was reversible after washout. The relative order of potency of the flavonoids was apigenin> or =genistein>quercetin>naringenin> or =rutin>catechin. Analysis of the chemical structure showed that the relaxant activity was progressively diminished by the prese…

Glucagon-like peptide-1 relaxes gastric antrum through nitric oxide in mice.

Abstract Glucagon-like-peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the intestinal enteroendocrine-L cells and released after meal ingestion. GLP-1 reduces postprandial glycemia not only by its hormonal effects, but also by its inhibitory effects on gastrointestinal motility. Recently, we showed that GLP-1 acts in the enteric nervous system of mouse intestine. Therefore our working hypothesis was that GLP-1 may have also a direct influence on the gastric mechanical activity since the major part of experimental studies about its involvement in the regulation of gastric motility have been conducted in in vivo conditions. The purposes of this study were (i) to examine exogen…

Effects of extract from Opuntia Ficus Indica Fruits on mouse ileal motility in vitro.

Effect of the GLP-1 analog liraglutide on satiation and gastric sensorimotor function during nutrient-drink ingestion

Background/Aim:Liraglutide, a glucagon-like peptide-1 analog, induces weight loss. We investigated whether liraglutide affects gastric accommodation and satiation by measuring the intragastric pressure (IGP) during nutrient-drink consumption and using the barostat technique.Methods:Ten healthy volunteers (HVs) were tested after placebo, 0.3, 0.6 or 1.2 mg liraglutide administration. IGP was studied during intragastric nutrient-drink (1.5 kcal ml(-1)) infusion (60 ml min(-1)), while the HVs scored their satiation on a graded scale until maximal satiation. In a separate session, isobaric distentions were performed using the barostat with stepwise increments of 2 mm Hg starting from minimal di…