PI 3‐kinase‐ and ERK‐MAPK‐dependent mechanisms underlie Glucagon‐Like Peptide‐1‐mediated activation of Sprague Dawley colonic myenteric neurons

2019 ◽  
Vol 31 (8) ◽  
Author(s):  
Rebecca O'Brien ◽  
Maria M. Buckley ◽  
Amy Kelliher ◽  
Dervla O'Malley
Keyword(s):  
Sprague Dawley ◽  
Myenteric Neurons ◽  
Erk Mapk ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Ameliorates the Development of Periodontitis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Noritaka Sawada ◽  
Kei Adachi ◽  
Nobuhisa Nakamura ◽  
Megumi Miyabe ◽  
Mizuho Ito ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Alveolar Bone ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Second Molar ◽  
Sd Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague–Dawley (SD) rats ( n = 30 ) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.

Glucagon-like peptide-1 response to whey protein is less diminished by dipeptidyl peptidase-4 in comparison with responses to dextrin, a lipid and casein in rats

2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yuki Shimizu ◽  
Hiroshi Hara ◽  
Tohru Hira
Keyword(s):  
Whey Protein ◽  
Dipeptidyl Peptidase ◽  
Dietary Proteins ◽  
Sprague Dawley ◽  
Dipeptidyl Peptidase 4 ◽  
Sprague Dawley Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Although glucose is the best-known nutrient to stimulate glucagon-like peptide-1 (GLP-1) secretion, dietary peptides also potently stimulate GLP-1 secretion. Certain peptide fragments derived from dietary proteins possess dipeptidyl peptidase-4 (DPP-4) inhibitory activity in vitro. Hence, we hypothesised that dietary peptides protect GLP-1 from degradation through attenuating DPP-4 activity in vivo. Here, we compared GLP-1 responses with dietary proteins, a carbohydrate and a lipid (Intralipos) in rats having or not having plasma DPP-4 activity. Plasma GLP-1 concentrations clearly increased by oral administration of whey protein (2–4 g/kg), but not by that of dextrin (2–4 g/kg), in control rats (untreated Sprague–Dawley rats and F344/Jcl rats), having DPP-4 activity. In contrast, dextrin administration increased the plasma GLP-1 concentrations as the whey protein administration did, in rats having reduced or no DPP-4 activity (a DPP-4 inhibitor, sitagliptin-treated Sprague–Dawley rats or DPP-4-deficient F344/DuCrl/Crlj rats). DPP-4 inhibition by sitagliptin treatment also enhanced GLP-1 response to Intralipos, and casein, but the treatment did not further enhance GLP-1 response to whey protein. Intestinal GLP-1 content and gastric emptying rate were not associated with differences in GLP-1 responses to test nutrients. The luminal contents from rats administered whey protein decreased DPP-4 activity in vitro. These results suggest that GLP-1 released by dextrin, Intralipos and casein was immediately degraded by DPP-4, while GLP-1 released by whey protein was less degraded. Our study provides novel in vivo evidence supporting the hypothesis that dietary peptides not only stimulate GLP-1 secretion but also inhibit DPP-4 activity to potentiate GLP-1 response.

scholarly journals The Potential of Hibiscus sabdariffa Linn in Inducing Glucagon-Like Peptide-1 via SGLT-1 and GLPR in DM Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Neng Tine Kartinah ◽  
Fadilah Fadilah ◽  
Ermita Ilyas Ibrahim ◽  
Yuliana Suryati
Keyword(s):  
Active Ingredient ◽  
Interaction Mechanism ◽  
Pancreatic Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hibiscus Sabdariffa ◽  
Sprague Dawley ◽  
Active Ingredients ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Increase Insulin Secretion

Background. Glucagon-like peptide 1 (GLP-1) hormone is an incretin hormone that is secreted in the ileum and plays a role in the pancreas to increase insulin secretion, stimulate proliferation, and prevent pancreatic β-cell apoptosis. Currently, diabetes mellitus (DM) treatment based on GLP-1 work is being developed, for instance, from herbal plants such as Hibiscus sabdariffa Linn (H. sabdariffa). Therefore, this study aims to determine the potential of H. sabdariffa in GLP-1 secretion in the ileum and its action in pancreatic β-cells. In addition, this study also aims to determine the active ingredients of H. sabdariffa (Hib) that interact with sodium-glucose cotransporter-1 (SGLT-1) so that it can increase GLP-1 secretion in the ileum and interact with GLP-1 receptors (GLP-1R) in the pancreas. Method. This experimental study used 24 experimental animals of Sprague–Dawley type (aged 8–10 weeks, weight 200–250 g) that were divided into 6 groups, namely, (i) normal (C), (ii) normal-Hib 200 (C-Hib200), (iii) normal-Hib 500 (C-Hib500), (iv) DM (C-DM), (v) DM-Hib200, and (vi) DM-Hib500. H. sabdariffa extract was given orally once a day for 5 weeks. Testing of GLP-1 levels in the ileum and pancreatic tissue was performed by enzyme-linked immunosorbent assay. The prediction of the interaction mechanism of the active substance H. sabdariffa against GLP-1 was done using molecular docking. Results. There was a decrease in GLP-1 levels in the ileum of DM rats (p<0.05). However, DM rats administered H. sabdariffa 500 mg/kg BW had GLP-1 levels that were the same as in normal rats (p>0.05). This is due to active ingredients such as leucosin, which binds to SGLT-1. Administration of 500 mg/kg BW H. sabdariffa in DM rats resulted in GLP-1 levels in the pancreas that were the same as in normal rats (p>0.05). In addition, the active ingredient of H. sabdariffa, delphinidin, binds to GLPR in the pancreas. Conclusion. The active ingredient of H. sabdariffa can increase GLP-1 secretion in the ileum and can interact with G protein-linked receptors in the pancreas.

scholarly journals The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats

2020 ◽  
Vol 21 (12) ◽  
pp. 4422
Author(s):  
Motoi Kobashi ◽  
Yuichi Shimatani ◽  
Masako Fujita ◽  
Yoshihiro Mitoh ◽  
Ryusuke Yoshida ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Nucleus Tractus Solitarius ◽  
Superior Laryngeal Nerve ◽  
Mutual Interaction ◽  
Sprague Dawley ◽  
Orexin A ◽  
Medial Nucleus ◽  
Sprague Dawley Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague–Dawley rats under urethane–chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested.

scholarly journals Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT2c) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward

2019 ◽  
Vol 20 (4) ◽  
pp. 889 ◽  
Author(s):  
Erin Howell ◽  
Hannah Baumgartner ◽  
Lia Zallar ◽  
Joaquín Selva ◽  
Liv Engel ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Receptor Agonist ◽  
Food Reinforcement ◽  
Progressive Ratio ◽  
Sprague Dawley ◽  
Operant Responding ◽  
Orexigenic Peptide ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

Current literature indicates that the orexigenic peptide ghrelin increases appetitive motivation via signaling in the mesolimbic reward system. Another gastric peptide, glucagon-like peptide-1 (GLP-1), and the neurotransmitter 5-hydroxytryptamine (5-HT), are both known to suppress operant responding for food by acting on key mesolimbic nuclei, including the ventral tegmental area (VTA). In order to investigate the interaction effects of ghrelin, GLP-1, and 5-HT within the VTA, we measured operant responding for sucrose pellets after the administration of ghrelin, the GLP-1 receptor agonist exendin-4 (Ex-4), and the 5-HT2c receptor agonist Ro60-0175 in male Sprague-Dawley rats. Following training on a progressive ratio 3 (PR3) schedule, animals were first injected with ghrelin into the VTA at doses of 3 to 300 pmol. In subsequent testing, separate rats were administered intraperitoneal (IP) Ex-4 (0.1–1.0 µg/kg) or VTA Ex-4 (0.01–0.1 µg) paired with 300 pmol ghrelin. In a final group of rats, the 5-HT2c agonist Ro60-0175 was injected IP (0.25–1.0 mg/kg) or into the VTA (1.5–3.0 µg), and under both conditions paired with 300 pmol ghrelin delivered into the VTA. Our results indicated that ghrelin administration increased operant responding for food reward and that this effect was attenuated by IP and VTA Ex-4 pretreatment as well as pre-administration of IP or VTA Ro60-0175. These data provide compelling evidence that mesolimbic GLP-1 and serotonergic circuitry interact with the ghrelinergic system to suppress ghrelin’s effects on the mediation of food reinforcement.

A functional role for central glucagon-like peptide-1 receptors in lithium chloride-induced anorexia

1999 ◽  
Vol 277 (5) ◽  
pp. R1537-R1540 ◽  
Author(s):  
Linda Rinaman
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Lithium Chloride ◽  
Neural Pathways ◽  
Sprague Dawley ◽  
Receptor Signalling ◽  
Sprague Dawley Rats ◽  
Licl Treatment ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The present study sought to determine whether central glucagon-like peptide-1 (GLP-1)-receptor signalling contributes to the anorexigenic effects of systemically administered lithium chloride (LiCl). Male Sprague-Dawley rats with chronic intracerebroventricular (ICV) cannulas were acclimated to a feeding schedule that included daily 30-min access to palatable mash. In the first experiment, ICV infusion of a GLP-1-receptor antagonist [exendin-4-(3—39)] significantly attenuated (10 μg dose) or completely blocked (20 μg dose) the inhibition of food intake produced by subsequent ICV infusion of GLP-1-(7—36) amide (5 μg). In the second experiment, rats were infused with 0, 10, or 20 μg of the GLP-1-receptor antagonist ICV, followed by injection of 0.15 M LiCl (50 mg/kg ip) or the same volume of 0.15 M NaCl. The ability of LiCl treatment to suppress food intake was significantly attenuated in rats that were pretreated with the GLP-1-receptor antagonist. These results support the view that central mechanisms underlying LiCl-induced anorexia include a prominent role for endogenous GLP-1 neural pathways.

scholarly journals Glucagon-like peptide-1 receptor agonist, exendin-4, reduces reinstatement of heroin seeking behavior in rats

2019 ◽  
Author(s):  
Joaquin E. Douton ◽  
Corinne Augusto ◽  
Brooke A Stultzfus ◽  
Nurgul Carkaci-Salli ◽  
Kent E. Vrana ◽  
...  
Keyword(s):  
Phase 1 ◽  
Phase 2 ◽  
Sprague Dawley ◽  
Nucleus Accumbens Shell ◽  
Self Administration ◽  
Phase 3 ◽  
Drug Induced ◽  
Seeking Behavior ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

AbstractBackgroundStudies have shown that ‘satiety’ agents such as exendin-4 (a glucagon-like peptide-1 analog) reduce responding for addictive drugs (e.g., cocaine, nicotine, alcohol). In this study we tested the effect of exendin-4 on cue-induced and drug-induced reinstatement of heroin seeking behavior in rats.MethodsThis study consisted of three phases: In Phase 1, 55 male Sprague-Dawley rats had 15 daily pairings of saccharin with heroin self-administration. In Phase 2, rats experienced a 16-day home cage abstinence period and daily treatment with vehicle or exendin-4. On day 17, an extinction/reinstatement test was performed to assess drug seeking. In Phase 3, rats experienced 9 days of extinction followed by a reinstatement only test. Finally, expression of mRNA for various receptors in the nucleus accumbens shell (NAcS) was measured using RTqPCR.ResultsIn Phase 1, rats that avoided intake of the heroin-paired saccharin cue exhibited shorter latency to obtain the first infusion. In Phase 2, treatment with exendin-4 decreased cue-induced, but not drug-induced heroin seeking. In Phase 3, saccharin avoiders previously treated with exendin-4 increased acceptance of saccharin, and 1-hour pretreatment with Exendin-4 abolished drug-induced heroin seeking. Finally, exendin-4 treatment increased expression of mRNA for the Orexin 1 receptor (OX1) in the NAcS, but did not affect expression of dopamine D2 receptors, GLP-1 receptors, or leptin receptors in this same structure.ConclusionExendin-4 reduced cue- and drug-induced heroin seeking and increased acceptance of the drug-associated saccharin cue. These changes in behavior were accompanied by an increase in the expression of the OX1 receptor in the NAcS.

scholarly journals Enhanced postprandial glucagon-like peptide-1 secretion during obesity development has a protective role against glucose intolerance induction in rats

2019 ◽  
Vol 122 (04) ◽  
pp. 411-422 ◽  
Author(s):  
Jukkrapong Pinyo ◽  
Tohru Hira ◽  
Hiroshi Hara
Keyword(s):  
Glucose Intolerance ◽  
Control Diet ◽  
Insulin Response ◽  
Postprandial Glucose ◽  
Control Group ◽  
Sprague Dawley ◽  
Glycaemic Response ◽  
Continuous Administration ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

AbstractGlucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial glycaemic response by enhancing insulin secretion. We previously demonstrated that the postprandial GLP-1 response was enhanced during the development of diet-induced obesity in rats. However, the physiological relevance of the enhanced GLP-1 response remained unclear. We aimed to determine the role of endogenous GLP-1 during obesity development. Male Sprague–Dawley rats were given either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose, weight basis) diet with or without continuous administration of the GLP-1 receptor antagonist, exendin (9–39) (Ex9, 100 µg/d), for 5 weeks. Meal tolerance tests (MTT) were performed to assess postprandial glucose, insulin and GLP-1 responses to a liquid diet administration (15 kcal (63 kJ)/10 ml per kg body weight) every 2 weeks. The AUC of postprandial glucose in the HFS group was similar to the control group in both MTT (P = 0·9665 and P = 0·3475, respectively), whereas AUC of postprandial GLP-1 (after 4 weeks,P = 0·0457) and of insulin (after 2 and 4 weeks, P = 0·0486 and P = 0·0110) was higher in the HFS group compared with the control group. In the Ex9 group, AUC of postprandial glucose (P = 0·0297 and P = 0·0486) was higher along with a lower insulin response compared with the HFS group (P = 0·0564 and P = 0·0281). These results suggest that enhancement of the postprandial GLP-1 response during obesity development has a role in maintaining a normal postprandial glycaemic response. Hence, enhancing endogenous GLP-1 secretion by certain materials could be a potential target for prevention of glucose intolerance.

scholarly journals Glucagon-Like Peptide-1 Receptor Agonist, Liraglutide, Attenuated Diabetic Retinal Edema in Spontaneously Diabetic Torii Fatty Rats

2021 ◽  
Author(s):  
Kazuho Inoue ◽  
Shohei Yamada ◽  
Seiko Hoshino ◽  
Minoru Watanabe ◽  
Kenjiro Kimura ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Receptor Agonist ◽  
Vehicle Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Retinal Edema ◽  
Monocyte Chemoattractant Protein 1 ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background: This study aims to investigate the effect of the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide on retinal edema as compared with insulin and hydralazine using an animal model of type 2 diabetes with obesity, hypertension, and hyperlipidemia.Methods: Male spontaneously diabetic Torii (SDT) fatty rats at 8 weeks of age were randomly assigned to three groups: the liraglutide group (SDT-lira, n = 6) received a subcutaneous injection of liraglutide from the age of 8 to 16 weeks, the SDT-ins-hyd group (n = 6) was provided both insulin against hyperglycemia and hydralazine against hypertension to match levels of both blood glucose and blood pressure to those of the liraglutide group, and the control group of SDT fatty rats (SDT-vehicle, n = 7) and a nondiabetic control group of Sprague–Dawley rats (SD, n = 7) were injected with vehicle only. Both eyeballs of all groups were collected at the age of 16 weeks.Results: Retinal thickness, which was found in the SDT-vehicle group, was significantly prevented to similar levels in both the SDT-lira and SDT-ins-hyd groups. Immunohistological analysis revealed that GLP-1 receptor was not expressed in the retina of all rats. The ocular protein expression of monocyte chemoattractant protein-1, which causes a proinflammatory situation, was significantly upregulated in all SDT fatty rats as compared to SD rats, but the expression levels were similar between all SDT fatty rats. With regard to neovascularization in the eyes, there were no significant differences in protein expressions of vascular endothelial growth factor, CD31, or endothelial nitric oxide synthase in all rats.Conclusions: The present study indicates that liraglutide prevents retinal thickening, dependent on blood glucose and blood pressure levels in SDT fatty rats without ocular neovascularization. However, the effects did not improve the ocular proinflammatory state.

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