• Title/Summary/Keyword: Glucagon-like Peptide 2

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Glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes

  • Lee, Seungah;Lee, Dong Yun
    • Annals of Pediatric Endocrinology and Metabolism
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    • v.22 no.1
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    • pp.15-26
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    • 2017
  • The prevalence of type 2 diabetes (T2D) is increasing worldwide. Patients with T2D suffer from various diabetes-related complications. Since there are many patients with T2D that cannot be controlled by previously developed drugs, it has been necessary to develop new drugs, one of which is a glucagon-like peptide-1 (GLP-1) based therapy. GLP-1 has been shown to ameliorate diabetes-related conditions by augmenting pancreatic ${\beta}-cell$ insulin secretion and having the low risk of causing hypoglycemia. Because of a very short half-life of GLP-1, many researches have been focused on the development of GLP-1 receptor (GLP-1R) agonists with long half-lives such as exenatide and dulaglutide. Now GLP-1R agonists have a variety of dosing-cycle forms to meet the needs of various patients. In this article, we review the physiological features of GLP-1, the effects of GLP-1 on T2D, the features of several GLP-1R agonists, and the therapeutic effect on T2D.

Protein-protein Interaction Analysis of Glucagon-like Peptide-2 Receptor with Its Native Ligand Glucagon-like Peptide-2

  • Nagarajan, Santhosh Kumar
    • Journal of Integrative Natural Science
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    • v.10 no.3
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    • pp.125-130
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    • 2017
  • Glucagon like pepide-2, one of the GLPs, is involved in various metabolic functions in the gastrointestinal tract. It plays a major role in the regulation of mucosal epithelium and the intestinal crypt cell proliferation. Because of their therapeutic importance towards the diseases in the gastrointestinal tract, it becomes necessary to study their interaction with its receptor, GLP-2R. In this study, we have developed protein-protein docking complexes of GLP-2 - GLP-2 receptor. Homology models of GLP-2 are developed, and a reliable model out of the predicted models was selected after model validation. The model was bound with the receptor, to study the important interactions of the complex. This study could be useful in developing novel and potent drugs for the diseases related with GLP-2.

Induction of insulin receptor substrate-2 expression by Fc fusion to exendin-4 overexpressed in E. coli: a potential long-acting glucagon-like peptide-1 mimetic

  • Kim, Jae-Woo;Kim, Kyu-Tae;Ahn, You-Jin;Jeong, Hee-Jeong;Jeong, Hyeong-Yong;Ryu, Seung-Hyup;Lee, Seung-Yeon;Lee, Chang-Woo;Chung, Hye-Shin;Jang, Sei-Heon
    • BMB Reports
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    • v.43 no.2
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    • pp.146-149
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    • 2010
  • Exendin-4 (Ex-4), a peptide secreted from the salivary glands of the Gila monster lizard, can increase pancreatic $\beta$-cell growth and insulin secretion by activating glucagon-like peptide-1 receptor. In this study, we expressed a fusion protein consisting of exendin-4 and the human immunoglobulin heavy chain (Ex-4/IgG-Fc) in E. coli and explored its potential therapeutic use for the treatment of insulin-resistant type 2 diabetes. Here, we show that the Ex-4/IgG-Fc fusion protein induces expression of insulin receptor substrate-2 in rat insulinoma INS-1 cells. Our findings therefore suggest that Ex-4/IgG-Fc overexpressed in E. coli could be used as a potential, long-acting glucagon-like peptide-1 mimetic.

Theoretical Protein Structure Prediction of Glucagon-like Peptide 2 Receptor Using Homology Modelling

  • Nagarajan, Santhosh Kumar;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.10 no.3
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    • pp.119-124
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    • 2017
  • Glucagon-like peptide 2 receptor, a GPCR, binds with the glucagon-like peptide, GLP-2 and regulates various metabolic functions in the gastrointestinal tract. It plays an important role in the nutrient homeostasis related to nutrient assimilation by regulating mucosal epithelium. GLP-2 receptor affects the cellular response to external injury, by controlling the intestinal crypt cell proliferation. As they are therapeutically attractive towards diseases related with the gastrointestinal tract, it becomes essential to analyse their structural features to study the pathophysiology of the diseases. As the three dimensional structure of the protein is not available, in this study, we have performed the homology modelling of the receptor based on single- and multiple template modeling. The models were subjected to model validation and a reliable model based on the validation statistics was identified. The predicted model could be useful in studying the structural features of GLP-2 receptor and their role in various diseases related to them.

A Novel 3-(8-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl Acetate Skeleton and Pharmacophore Model as Glucagon-like Peptide 1 Receptor Agonists

  • Gong, Young-Dae;Cheon, Hyae-Gyeong;Lee, Tae-Ho;Kang, Nam-Sook
    • Bulletin of the Korean Chemical Society
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    • v.31 no.12
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    • pp.3760-3764
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    • 2010
  • We screened 10,000 heterocyclic small molecules and identified a novel hit core skeleton of 3-(8-chloro-6-(trifluoromethyl) imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives. It has been selected as a potential glucagon-like peptide 1 receptor (GLP-1R) activator and demonstrated its effects in increasing GLP-1 secretion, and thereby increasing the glucose responsiveness in both in vitro and pharmacology analyses. Further studies are currently underway to optimize the potency and selectivity of 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives (hit compounds 2 and 8), and address their in vivo efficacy and therapeutic potential. These molecules may serve as useful evidence showing that compounds with a 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate moiety are selective GLP-1R agonists, and have potential as anti-diabetic treatment agents.

Incretin-based Treatment for Type 2 Diabetes Mellitus (제2형 당뇨병 환자에게 인크레틴 기반 약물치료요법)

  • Kim, Hyun-Ah;Kim, Hun-Sung
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.57-65
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    • 2011
  • Incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide delay gastric emptying, increasing satiety, and enhance insulin secretion. Two new classes of treatments related to incretin hormones for the management of type 2 diabetes mellitus have emerged: GLP-1 receptor agonists (e.g., exenatide, liraglutide) and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin, saxagliptin, vildagliptin, alogliptin), which prevent the degradation of GLP-1. A MEDLINE search was conducted in order to evaluate the efficacy and safety of incretin-based therapies and publications were reviewed. Data from clinical trials indicated incretin-based treatment showed clinically significant reductions in hemoglobin A1c with low risk of hypoglycemia. Weight reductions were observed with GLP-1 receptor agonists where as DPP-4 inhibitors are weight neutral.

Morbidly Obese Patients Treated Obesity and Metabolic Diseases Using Naltrexone/Bupropion Extended Release and Other Drugs of Various Mechanisms (날트렉손/부프로피온 복합제 및 여러 기전의 약물을 이용하여 비만과 동반 대사질환을 치료한 고도비만환자)

  • Cho, Soo Hyun
    • Archives of Obesity and Metabolism
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    • v.1 no.2
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    • pp.83-88
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    • 2022
  • Obesity increases the risk of developing metabolic diseases such as hypertension, type 2 diabetes, hyperlipidemia, and cardiovascular diseases, as well as some cancers. To prevent the occurrence of these diseases and death, it is essential to manage obesity. Though there are several treatments for obesity, lifestyle interventions, such as diet and exercise, and drug therapy are most widely used in clinical practice. Among the anti-obesity drugs available, the weight loss effect of naltrexone/bupropion has been well-proven. We present a case study in which naltrexone/bupropion, a glucagon-like peptide-1 agonist, and a sodium-glucose transporter 2 inhibitor showed significant weight loss and improved metabolic parameters. Additionally, the management of type 2 diabetes and hypertension, which are common diseases in patients with obesity, was also included.

Case of Effective Treatment using Glucagon-Like Peptide-1 Receptor Agonist in Patient with Obesity and Non-Alcoholic Fatty Liver Disease (비알코올지방간질환을 동반한 비만 환자에서 Glucagon-Like Peptide-1 수용체작용제를 이용한 효과적인 치료 증례)

  • Tae Sic Lee
    • Archives of Obesity and Metabolism
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    • v.2 no.2
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    • pp.71-75
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    • 2023
  • Obesity is closely related to chronic diseases and cancer. The present case report aims to discuss the anti-obesity treatment strategy and the evaluation of the clinical progress in a patient with obesity and concurrent fatty liver disease. Following five months of treatment with liraglutide and rosuvastatin, the patient had a weight reduction of 3 kg (4.7%), a decrease in fasting blood sugar by 42 mg/dl (26.6%), a decrease in low-density lipoprotein cholesterol by 82 mg/dl (60.2%), and decrease in alanine transaminase. This case report documented the treatment of a patient with common chronic diseases encountered in the outpatient setting. Based on the therapeutic effects documented in clinical and laboratory indices, the anti-obesity treatment plan significantly aided in managing chronic diseases.

The Effects of Glucagon-like Peptide-2 on the Tight Junction and Barrier Function in IPEC-J2 Cells through Phosphatidylinositol 3-kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling Pathway

  • Yu, Changsong;Jia, Gang;Deng, Qiuhong;Zhao, Hua;Chen, Xiaoling;Liu, Guangmang;Wang, Kangning
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.5
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    • pp.731-738
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    • 2016
  • Glucagon-like peptide-2 (GLP-2) is important for intestinal barrier function and regulation of tight junction (TJ) proteins, but the intracellular mechanisms of action remain undefined. The purpose of this research was to determine the protective effect of GLP-2 mediated TJ and transepithelial electrical resistance (TER) in lipopolysaccharide (LPS) stressed IPEC-J2 cells and to test the hypothesis that GLP-2 regulate TJ and TER through the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway in IPEC-J2 cells. Wortmannin and LY294002 are specific inhibitors of PI3K. The results showed that $100{\mu}g/mL$ LPS stress decreased TER and TJ proteins occludin, claudin-1 and zonula occludens protein 1 (ZO-1) mRNA, proteins expressions (p<0.01) respectively. GLP-2 (100 nmol/L) promote TER and TJ proteins occludin, claudin-1, and zo-1 mRNA, proteins expressions in LPS stressed and normal IPEC-J2 cells (p<0.01) respectively. In normal cells, both wortmannin and LY294002, PI3K inhibitors, prevented the mRNA and protein expressions of Akt and mTOR increase induced by GLP-2 (p<0.01) following with the significant decreasing of occludin, claudin-1, ZO-1 mRNA and proteins expressions and TER (p<0.01). In conclusion, these results indicated that GLP-2 can promote TJ's expression and TER in LPS stressed and normal IPEC-J2 cells and GLP-2 could regulate TJ and TER through the PI3K/Akt/mTOR pathway.

Ca2+ entry through reverse Na+/Ca2+ exchanger in NCI-H716, glucagon-like peptide-1 secreting cells

  • Choi, Kyung Jin;Hwang, Jin Wook;Kim, Se Hoon;Park, Hyung Seo
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.3
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    • pp.219-225
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    • 2022
  • Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca2+ elevation, the stimulus-secretion pathway is not completely understood yet. Therefore, the aim of this study was to investigate the role of reverse Na+/Ca2+ exchanger (rNCX) in Ca2+ entry induced by muscarinic stimulation in NCI-H716 cells, a human enteroendocrine GLP-1 secreting cell line. Intracellular Ca2+ was repetitively oscillated by the perfusion of carbamylcholine (CCh), a muscarinic agonist. The oscillation of cytosolic Ca2+ was ceased by substituting extracellular Na+ with Li+ or NMG+. KB-R7943, a specific rNCX blocker, completely diminished CCh-induced cytosolic Ca2+ oscillation. Type 1 Na+/Ca2+ exchanger (NCX1) proteins were expressed in NCI-H716 cells. These results suggest that rNCX might play a crucial role in Ca2+ entry induced by cholinergic stimulation in NCI-H716 cells, a GLP-1 secreting cell line.