GLTP1 Antibody
Description
Definition and Biological Relevance of GLP-1R Antibodies
GLP-1R antibodies are monoclonal or polyclonal antibodies designed to target the glucagon-like peptide-1 receptor (GLP-1R), a G protein-coupled receptor (GPCR) involved in glucose homeostasis, insulin secretion, and anti-inflammatory responses . These antibodies are used for:
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Research: Detecting receptor expression in tissues (e.g., pancreatic β-cells, neurons) .
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Therapeutics: Antagonizing or agonizing GLP-1R to treat metabolic disorders like diabetes, obesity, and congenital hyperinsulinism .
Development of GLP-1R Antibodies
Key advancements in antibody development include:
Antibody Screening and Engineering
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Phage Display Libraries: Used to isolate high-affinity single-chain variable fragments (ScFvs) against GLP-1R . For example, Glp1R0017 (IC₅₀ = 5.2 nmol/L) showed cross-species antagonism in mice, rats, and humans .
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Synthetic DNA Platforms: Twist Bioscience’s GPCR antibody library enabled the development of TB-222-023, a potent antagonist with superior efficacy compared to peptide-based inhibitors like Exendin .
Table 1: Key GLP-1R Antibodies and Their Applications
Therapeutic Mechanisms
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Antagonists: Reverse glucose-lowering effects of GLP-1 agonists (e.g., liraglutide) by blocking receptor signaling .
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Agonists: Enhance insulin secretion via cAMP/PKA pathways, promoting β-cell survival .
Mechanistic Insights from Preclinical Studies
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Metabolic Effects: Chronic GLP-1R activation increases glycolysis and ATP production in β-cells via mTOR/HIF-1α pathways .
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Anti-Inflammatory Action: Antibodies like exendin-4 reduce NF-κB activation, lowering pro-inflammatory cytokines in intestinal diseases .
Future Directions
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- In Arabidopsis thaliana, AtGLTP1, along with At1g21360 and At3g21260, forms a small gene family that is homologous to the mammalian glycosphingolipid transfer protein. (PMID: 18537822)
Q&A
Here’s a structured FAQ collection for researchers focusing on GLP-1 antibodies in academic contexts, synthesized from peer-reviewed studies and technical reports:
Advanced Research Challenges
How can researchers resolve contradictions in GLP-1 antibody efficacy across preclinical models?
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Analytical framework:
What strategies mitigate antibody-induced receptor internalization in live-cell assays?
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Use pH-sensitive fluorescent tags (e.g., pHrodo) to track internalization dynamics .
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Co-administer lysosomal inhibitors (e.g., chloroquine) to preserve surface receptor levels .
How do researchers address batch variability in anti-GLP-1 antibody production?
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Implement orthogonal characterization:
Methodological Insights from Recent Studies
Designing cross-reactive antibodies for translational studies:
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Phage display libraries with diversity-enhancing CDR regions (e.g., Twist Bioscience’s GPCR library) enable isolation of antibodies binding human/mouse GLP-1R .
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Example: Glp1R0017 antibody antagonizes GLP-1R in 5 species (human, mouse, rat, dog, cynomolgus) with IC50 ≤ 2 nM .
Optimizing antibody-drug conjugates (ADCs) for GLP-1 delivery:
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Covalent "painting" via reactive peptides (e.g., MIT-PEP sequence) achieves >40% antibody-drug coupling efficiency at 37°C .
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In vivo results: Single ADC dose in obese mice reduced body weight by 12% over 15d vs. 6% with free drug .
Data Discrepancy Analysis
Conflicting reports on GLP-1 antibody-mediated insulin secretion:
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Root cause: Differences in assay glucose concentrations (5 mM vs. 11 mM) alter glucose-dependent activity .
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Recommendation: Standardize glucose levels (8–10 mM) and include GLP-1R-negative controls .
