Glucagon-like peptide-1 receptor agonist exendin-4 mitigates lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages.

Glucagon-like peptide-1 receptor agonist exendin-4 mitigates lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages. Int Immunopharmacol. 2019 Nov 01;:105969 Authors: Lu C, Xie T, Guo X, Wu D, Li S, Li X, Lu Y, Wang X Abstract Macrophages play a critical role in the immune response against pathogen invasion and injury. However, under pathological stress, macrophages could have aberrant roles and contribute to the pathogenesis of inflammatory associated diseases. Exenatide is a glucagon-like peptide 1(GLP-1) agonist, which belongs to the family of synthetic exendin-based incretin mimetic. Exendin related compounds reduce glucose levels in type 2 diabetes patients. The purpose of this study was to examine the anti-inflammatory effects of exendin-4 in LPS-induced activation of macrophages. We show that exendin-4 inhibits LPS-induced expression of inflammatory mediators (iNOS, COX-2, PGE2 and NO) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in RAW264.7 macrophages. Exendin-4 pretreatment mitigates LPS induced cellular ROS production. Mechanistically, Exendin-4 suppresses the LPS-induced activation of the JNK and AP-1 pathway. Furthermore, exendin-4 suppresses both nuclear p65 accumulation and transfected NF-κB promoter activity, indicating it inhibits the activation of the NF-κB pathway. Our study demonstrates that the GLP-1 agonist exendin-4 has a potent anti-inflammatory effect independent on its glucose...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research

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ConclusionsRepeated administration of DR1060 provides potent and sustained glycemic control and body weight loss effect in high-fat DIO mice. DR10601 is a promising long-acting agent deserving further investigation for the treatment of type 2 diabetes and obesity.
Source: Journal of Endocrinological Investigation - Category: Endocrinology Source Type: research
Purpose of review Incretin-based therapies mimic or augment the gut-hormone glucagon-like peptide (GLP)-1 and, due to their glucose-lowering potential and beneficial safety profile, as well as their cardiovascular safety and/or protection, are prescribed on a large scale to treat individuals with type 2 diabetes (T2D). However, whether the two drug-classes that belong to this category, respectively GLP-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, also reduce the risk of diabetic kidney disease (DKD) is at present heavily debated. This review aims to discuss the current evidence. Recent findings Evi...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: HORMONES, AUTACOIDS, NEUROTRANSMITTERS AND GROWTH FACTORS: Edited by Mark Cooper and Merlin Thomas Source Type: research
Publication date: Available online 20 November 2019Source: PeptidesAuthor(s): Sravan K. Thondam, Daniel J. Cuthbertson, John P.H. WildingAbstractGlucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide (GLP-1) are the two incretin hormones secreted by the enteroendocrine system in response to nutrient ingestion. Compared with GLP-1, GIP is less well studied as a hormone or as a potential pharmacological treatment. Beyond its insulinotropic effects in the pancreas, GIP has important biological actions in many other tissues but its role in dietary fat metabolism and lipid storage in adipose tissue has bee...
Source: Peptides - Category: Biochemistry Source Type: research
Publication date: Available online 19 November 2019Source: PeptidesAuthor(s): Clifford J. BaileyAbstractThe potential application of glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide, GIP) in the management of obesity and type 2 diabetes has been controversial. Initial interest in the therapeutic use of GIP was dampened by evidence that its insulinotropic activity was reduced in type 2 diabetes and by reports that it increased glucagon secretion and adipose deposition in non-diabetic individuals. Also, attention was diverted away from GIP by the successful development of glucagon-like peptide-1 (...
Source: Peptides - Category: Biochemistry Source Type: research
Obesity and related metabolic disorders, including type 2 diabetes mellitus (T2DM), alarmingly grow up in the modern society thus representing a serious issue for endocrinology and medicine. Obesity is the major risk factor for T2DM [1], however, not all obese individuals ultimately develop T2DM. Nevertheless, mechanisms linking obesity to T2DM are being extensively studied.
Source: Diabetes Research and Clinical Practice - Category: Endocrinology Authors: Source Type: research
Publication date: Available online 7 November 2019Source: PeptidesAuthor(s): Carolyn F DeaconAbstractGlucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with insulinotropic and glucagonotropic actions, and is believed to be the more physiologically important incretin hormone in healthy humans. Together with the other incretin hormone, glucagon-like peptide-1 (GLP-1), it plays an important role in regulating glucose homeostasis. Both GLP-1 and GIP are substrates of the enzyme dipeptidyl peptidase-4 (DPP-4), and DPP-4 inhibitors, which potentiate their effects on glycaemic control, are now used t...
Source: Peptides - Category: Biochemistry Source Type: research
ConclusionsOur findings suggest that, in an unselected population, the use of both classes of incretin-based medications is not associated with an increased risk of cholangiocarcinoma.
Source: Acta Diabetologica - Category: Endocrinology Source Type: research
Publication date: Available online 3 November 2019Source: PeptidesAuthor(s): Lærke S. Gasbjerg, Natasha C. Bergmann, Signe Stensen, Mikkel B. Christensen, Mette M. Rosenkilde, Jens J. Holst, Michael Nauck, Filip K. KnopAbstractGlucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) potentiate glucose-induced insulin secretion and are therefore thought to be responsible for the incretin effect. The magnitude of the incretin effect, defined as the fraction of postprandial insulin secretion stimulated by intestinal factors, has been reported to be up to ∼60% in healthy individuals. In ...
Source: Peptides - Category: Biochemistry Source Type: research
Publication date: Available online 25 October 2019Source: PeptidesAuthor(s): M.A. Nauck, H. Holle, M. Kahle, A. Tytko, C.F. Deacon, J.J. Holst, J.J. MeierAbstractBackground, aimsIn patients with type 2 diabetes, the lost insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is more apparent after continuous versus bolus administration. To test whether the difference might be explained by rapid tachyphylaxis in response to elevated concentrations of GIP, and whether patients with type 2 diabetes and their relatives are more susceptible to tachyphylaxis than healthy subjects.Patient...
Source: Peptides - Category: Biochemistry Source Type: research
Abstract BACKGROUND: To investigate the metabolic effects of FFAR4-selective agonists on islet and enteroendocrine cell hormone release and the combined therapeutic effectiveness with DPP-IV inhibitors. METHODS: Insulinotropic activity and specificity of FFAR4 agonists were determined in clonal pancreatic BRIN-BD11 cells. Expression of FFAR4 was assessed by qPCR and western blotting following agonist treatment in BRIN-BD11 cells and by immunohistochemistry in mouse islets. Acute in-vivo effects of agonists was investigated after intraperitoneal (i.p.) or oral administration in lean and HFF-obese diabetic mice...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research
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