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

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.

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Noritaka Sawada ◽  
Kei Adachi ◽  
Nobuhisa Nakamura ◽  
Megumi Miyabe ◽  
Mizuho Ito ◽  
...  

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.


1996 ◽  
Vol 271 (3) ◽  
pp. E458-E464 ◽  
Author(s):  
C. F. Deacon ◽  
L. Pridal ◽  
L. Klarskov ◽  
M. Olesen ◽  
J. J. Holst

Glucagon-like peptide 1 (GLP-1) metabolism was studied in halothane-anesthetized pigs (n = 7) using processing-independent (PI) and COOH-terminal (C) radioimmunoassays (RIA) and an enzyme-linked immunosorbent assay (ELISA) specific for biologically active GLP-1. Renal extraction of endogenous GLP-1 was detected by PI-RIA (33.1 +/- 13.3%) and C-RIA (16.0 +/- 6.3%) and by all assays during GLP-1 infusion (ELISA, 69.4 +/- 6.3%; PI-RIA, 32.6 +/- 7.3%; C-RIA, 43.7 +/- 3.4%), indicating substantial fragmentation. Hepatic and pulmonary degradation were undetectable under basal conditions, but exogenous GLP-1 elimination by the liver (43.6 +/- 8.9%) and lungs (10.1 +/- 3.2%) was measured by ELISA, suggesting primarily NH2-terminal degradation. Endogenous GLP-1 extraction by the hindleg was only detected by C-RIA (16.0 +/- 6.3%). During GLP-1 infusion, greater hindleg extraction was measured by ELISA (38.5 +/- 6.8%) and C-RIA (33.0 +/- 6.4%) than by PI-RIA (11.4 +/- 3.2%), indicating limited degradation at each terminus or more substantial COOH-terminal degradation. A shorter (P < 0.01) plasma half-life was revealed by ELISA (1.5 +/- 0.4 min) than by PI-RIA (4.5 +/- 0.6 min) or C-RIA (4.1 +/- 0.5 min). Metabolic clearance rates measured by PI-RIA (20.0 +/- 3.8 ml.min-1.kg-1) and C-RIA (15.5 +/- 1.6 ml.min-1.kg-1) were shorter (P < 0.01) than that measured by ELISA (106.8 +/- 14.7 ml.min-1.kg-1). Tissue-specific differential metabolism of GLP-1 occurs, and NH2-terminal degradation, rendering GLP-1 inactive, is particularly important in its clearance.


2021 ◽  
Vol 16 (11) ◽  
pp. 1934578X2110403
Author(s):  
Yan Ren ◽  
Wenwen Jiang ◽  
Chunli Luo ◽  
Xiaohan Zhang ◽  
Mingjin Huang

Atractylodes macrocephala ( AM) is a famous traditional Chinese medicine for intestinal epithelial restitution through activating Ca2+ channels. However, the roles of specific AM compositions in intestinal epithelial restitution are sparse. Therefore, this study aimed to compare the concrete effects of the 4 active ingredients (atractylon, β-eudesmol, atractylenolide II, atractylenolide III) of AM and their combination on intestinal epithelial repair and the Ca2+ pathway in intestinal epithelial cell (IEC-6) cells. First, the best combination of the 4 ingredients with an optimal mixing ratio of atractylon: β-eudesmol: atractylenolide II: atractylenolide III = 1:2:2:2 was demonstrated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide orthogonal experiment. Subsequently, enzyme-linked immunosorbent assay was used to measure anti-inflammatory cytokine levels, the migratory ability was evaluated by cell scratch experiments, cell cycle analysis and [Ca2+]cyt concentration in cells were detected by flow cytometry, and the expression of the Ca2+ pathway-related genes was detected by immunofluorescence staining, quantitative polymerase chain reaction and whole blood assays. Our result showed that atractylon, β-Eudesmol, atractylenolide II, and atractylenolide III showed different abilities to promote the IEC-6 cells proliferation, migration, and the expression of anti-inflammatory cytokines interleukin (IL)-2, IL-10, and ornithine decarboxylase, as well as the intracellular [Ca2+]cyt concentration through stromal interaction molecule 1 transposition to activate Ca2+ pathway. Thereinto, atractylenolide III was the main active ingredient of AM for pro-proliferation and anti-inflammation, and the combination of 4 AM ingredients performed better beneficial effects on IEC-6 cells. Therefore, our study suggested that atractylenolide III was the active ingredient of AM for intestinal epithelial repair through activating the Ca2+ pathway, and the 4 ingredients of AM have a synergy in intestinal epithelial repair.


Author(s):  
Eli Ben-Chetrit ◽  
Ami Ben Yaa'cov ◽  
Ahamad Quiteineh ◽  
Ohad Atia ◽  
Eran Regev ◽  
...  

Purpose: Anosmia and dysgeusia (AD) are common among COVID-19 patients. These symptoms are not frequently associated with rhinorrhea or nasal congestion and the underlying mechanism is unclear. Previous reports suggested that Glucagon-like peptide-1 (GLP-1) signaling plays a role in the modulation of olfaction and geusia. We aimed to assess the correlation between GLP-1 and COVID-19-associated AD. Methods: Blood samples obtained from COVID-19 patients with and without AD were tested for serum GLP-1 levels using enzyme-linked immunosorbent assay (ELISA). A second control group comprised of COVID-19-negative volunteers. Results: Forty-nine subjects were included in the study. Nineteen were positive for COVID-19. Of the 19 patients, ten had AD and nine declined such complaints. Age and basic metabolic rate were similar among all study groups. Serum GLP-1 levels were significantly lower among patients with AD as compared with patients without AD and COVID-19-negative individuals (1820 pg/ml vs 3536 pg/ml vs 3014 pg/ml, respectively, p<0.02). Conclusion: COVID-19 patients who reported of AD had lower serum levels of GLP-1 as compared with those lacking AD symptoms and COVID-19-negative individuals. These results suggest that GLP-1 may be involved in the pathogenesis of AD. However, further larger scale studies should corroborate our findings


2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yuki Shimizu ◽  
Hiroshi Hara ◽  
Tohru Hira

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.


2016 ◽  
Vol 310 (1) ◽  
pp. G26-G33 ◽  
Author(s):  
Yanan Hou ◽  
Stephen A. Ernst ◽  
Kaeli Heidenreich ◽  
John A. Williams

Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone that can act through its receptor (GLP-1R) on pancreatic β-cells and increase insulin secretion and production. GLP-1R agonists are used clinically to treat type 2 diabetes. GLP-1 may also regulate the exocrine pancreas at multiple levels, including inhibition through the central nervous system, stimulation indirectly through insulin, and stimulation directly on acinar cells. However, it has been unclear whether GLP-1R is present in pancreatic acini and what physiological functions these receptors regulate. In the current study we utilized GLP-1R knockout (KO) mice to study the role of GLP-1R in acinar cells. RNA expression of GLP-1R was detected in acutely isolated pancreatic acini. Acinar cell morphology and expression of digestive enzymes were not affected by loss of GLP-1R. GLP-1 induced amylase secretion in wild-type (WT) acini. In GLP-1R KO mice, this effect was abolished, whereas vasoactive intestinal peptide-induced amylase release in KO acini showed a pattern similar to that in WT acini. GLP-1 stimulated cAMP production and increased protein kinase A-mediated protein phosphorylation in WT acini, and these effects were absent in KO acini. These data show that GLP-1R is present in pancreatic acinar cells and that GLP-1 can regulate secretion through its receptor and cAMP signaling pathway.


2020 ◽  
Vol 21 (12) ◽  
pp. 4422
Author(s):  
Motoi Kobashi ◽  
Yuichi Shimatani ◽  
Masako Fujita ◽  
Yoshihiro Mitoh ◽  
Ryusuke Yoshida ◽  
...  

(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.


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