Related Experiment Video

Updated: Feb 28, 2026

Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
09:15

Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles

Published on: November 10, 2017

15.2K

The GLP-1 analogue lixisenatide decreases atherosclerosis in insulin-resistant mice by modulating macrophage

Ángela Vinué1, Jorge Navarro1,2,3, Andrea Herrero-Cervera1

  • 1Institute of Health Research-INCLIVA, Avda Menéndez Pelayo 4, 46010, Valencia, Spain.

Diabetologia
|June 14, 2017
PubMed
Abstract

Insights

Glucagon-like peptide-1 (GLP-1) analogues like lixisenatide reduce cardiovascular risk in type 2 diabetes by stabilizing atherosclerotic plaques. This occurs through reprogramming macrophages to an anti-inflammatory M2 phenotype, reducing plaque inflammation and size.

Area of Science:

  • Cardiovascular Research
  • Metabolic Diseases
  • Immunology

Background:

  • Glucagon-like peptide-1 (GLP-1) analogues are known to prevent cardiovascular events in type 2 diabetes mellitus.
  • The precise mechanisms underlying these cardioprotective effects, particularly concerning insulin resistance and atherosclerosis, remain largely unknown.

Purpose of the Study:

  • To investigate the impact of GLP-1 analogues on insulin resistance and atherosclerosis.
  • To elucidate the underlying molecular mechanisms, focusing on inflammatory pathways within macrophages.

Main Methods:

  • Atherosclerosis development was studied in Apoe-/- Irs2+/- mice treated with lixisenatide or liraglutide.
  • In vitro studies on macrophages from these mice were conducted to analyze inflammatory pathways.
  • Key markers of inflammation, macrophage phenotype, and plaque stability were assessed.

Main Results:

  • Lixisenatide and liraglutide improved glucose metabolism and blood pressure, independent of weight loss.
  • Both analogues significantly reduced atheroma plaque size.
  • Lixisenatide promoted stable atheromas with reduced inflammation, decreased IL-6, and modulated macrophage polarization towards an M2 phenotype.

Conclusions:

  • Lixisenatide reduces atheroma plaque size and instability by reprogramming macrophages to an M2 phenotype, thereby decreasing inflammation.
  • This study provides novel mechanistic insights into how GLP-1 analogues reduce cardiovascular risk in insulin-resistant individuals.
Keywords:
AtherosclerosisGLP-1InflammationMacrophageSTAT

More Related Videos

Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis NASH Resolution04:14

Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis NASH Resolution

Published on: April 16, 2019

12.8K
Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice09:06

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice

Published on: February 20, 2019

8.9K

Related Concept Videos

Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
1.1K
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
787
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
520
Inflammation01:38

Inflammation

Overview
62.8K
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
684
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
760