Related Experiment Video
Updated: Nov 2, 2025

Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice
Published on: March 20, 2017
GIPR antagonist antibodies conjugated to GLP-1 peptide are bispecific molecules that decrease weight in obese mice
Shu-Chen Lu1, Michelle Chen1, Larissa Atangan1
1Amgen Research, Department of Cardiometabolic Disorders, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
Abstract:
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) regulate glucose and energy homeostasis. Targeting both pathways with GIP receptor (GIPR) antagonist antibody (GIPR-Ab) and GLP-1 receptor (GLP-1R) agonist, by generating GIPR-Ab/GLP-1 bispecific molecules, is an approach for treating obesity and its comorbidities. In mice and monkeys, these molecules reduce body weight (BW) and improve many metabolic parameters. BW loss is greater with GIPR-Ab/GLP-1 than with GIPR-Ab or a control antibody conjugate, suggesting synergistic effects. GIPR-Ab/GLP-1 also reduces the respiratory exchange ratio in DIO mice. Simultaneous receptor binding and rapid receptor internalization by GIPR-Ab/GLP-1 amplify endosomal cAMP production in recombinant cells expressing both receptors. This may explain the efficacy of the bispecific molecules. Overall, our GIPR-Ab/GLP-1 molecules promote BW loss, and they may be used for treating obesity.
Related Concept Videos
Glucagon-like Receptor Agonists
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...
Dipeptidyl Peptidase 4 Inhibitors
Oral Hypoglycemic Agents: Glinides
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are...
Oral Hypoglycemic Agents: Biguanides and Glitazones
GPCRs Regulate Adenylyl Cylase Activity

