GPL1 Antibody
Description
Introduction to GLP-1 Antibodies
GLP-1 (Glucagon-like peptide-1) antibodies are specialized reagents or therapeutic agents targeting either the GLP-1 peptide itself or its receptor (GLP-1R). These antibodies play critical roles in research, diagnostics, and treatment of metabolic disorders. GLP-1 is a 30–31 amino acid incretin hormone secreted by intestinal L-cells, regulating glucose-dependent insulin secretion, gastric emptying, and appetite . Antibodies targeting GLP-1 or GLP-1R are engineered to modulate its activity, serving as tools for studying its physiological roles or as therapeutic agents for conditions like type 2 diabetes, obesity, and hyperinsulinism.
Types of GLP-1 Antibodies
GLP-1 antibodies are broadly categorized into two functional groups:
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Anti-GLP-1 Antibodies: Polyclonal or monoclonal antibodies raised against specific GLP-1 epitopes (e.g., AA 7–36, 1–31) for immunoassays. These are critical for quantifying GLP-1 in clinical or experimental settings .
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GLP-1R Antibodies: Engineered to bind GLP-1R, either mimicking (agonist) or blocking (antagonist) GLP-1’s action. These are synthetic or monoclonal antibodies developed via phage display libraries .
Therapeutic Applications of GLP-1R Antibodies
GLP-1R antibodies are advancing as next-generation therapies for metabolic and endocrine disorders.
GLP-1R Agonists
These antibodies enhance GLP-1R signaling, mimicking endogenous GLP-1’s effects:
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GLucose-Dependent Insulin Secretion: Activate β-cell cAMP/PKA pathways to stimulate insulin release .
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Weight Loss: Promote satiety via hypothalamic GLP-1R activation, slowing gastric emptying .
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Cardiovascular Benefits: Improve endothelial function and reduce atherosclerosis .
Examples:
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TB-001-003/TB-222-023: Synthetic antibodies developed using GPCR-focused libraries, showing superior efficacy to peptide agonists like exendin-4 in preclinical models .
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Dual GLP-1/FGF21 Receptor Agonists: In development for enhanced metabolic effects .
GLP-1R Antagonists
These antibodies block GLP-1R, useful for conditions requiring reduced insulin secretion:
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Congenital Hyperinsulinism: TB-222-023 demonstrated efficacy in inhibiting excessive insulin release in mouse models and human pancreatic islets .
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Hypoglycemia Management: Potential use in post-bariatric surgery hypoglycemia .
Development and Design
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Synthetic Libraries: Twist Bioscience’s GPCR-focused library incorporates endogenous ligand motifs into antibody heavy chains, enabling high-affinity GLP-1R binding. Antibodies with GLP-1 or GLP-2 motifs in HCDR3 domains showed antagonistic activity, while a GLP-1 peptide fusion enabled agonism .
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In Vitro & In Vivo Validation:
Immunogenicity and Challenges
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Antibody Formation: GLP-1 agonists like exenatide trigger anti-drug antibodies (ADAs) in up to 44% of patients, potentially reducing efficacy .
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Cross-Reactivity: Anti-GLP-1 antibodies may show limited cross-reactivity with GLP-2 (1% in some cases) .
Table 1: GLP-1R Antibody Therapeutic Applications
Table 2: Comparison of GLP-1R Antibodies vs. Peptide Agonists
Challenges and Future Directions
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Immunogenicity: ADA formation remains a concern, though humanized antibodies may mitigate this .
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Delivery Innovations: In vivo antibody painting, where GLP-1 is covalently linked to endogenous IgG, enhances stability and reduces dosing frequency .
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Dual Targeting: Combining GLP-1R agonism with other pathways (e.g., FGF21) may optimize therapeutic outcomes .
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- GeBP/GPLs regulate a subset of genes within the CPR5 pathway. [GPL1] PMID: 21875893
Q&A
FAQs for GLP-1 Antibody Research
(Note: Assumed "GPL1" refers to GLP-1 [glucagon-like peptide-1], as no "GPL1" term exists in indexed research literature.)
How to validate antibody specificity for GLP-1 receptor (GLP-1R) detection in preclinical models?
Validation requires three orthogonal methods:
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Immunohistochemistry with knockout controls (e.g., GLP-1R⁻/⁻ mice) to confirm absence of nonspecific binding .
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Competitive binding assays using recombinant GLP-1R extracellular domain (ECD) to block antibody-epitope interactions .
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Functional validation via cAMP assays in GLP-1R-transfected HEK293 cells, correlating antibody binding with receptor activation (EC₅₀ ~0.3–1.2 nM) .
Common pitfalls: Cross-reactivity with homologous receptors (e.g., GIPR) due to shared structural motifs in ECDs.
What methodological challenges arise when quantifying GLP-1R expression in non-pancreatic tissues?
Key challenges include:
What in vivo conjugation strategies improve GLP-1 antibody pharmacokinetics?
The antibody painting platform enables covalent drug attachment to endogenous IgGs:
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Electrophilic peptide design:
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Dose optimization:
How to design experiments assessing GLP-1 antibody effects on metabolic-inflammatory crosstalk?
Adopt a multi-omics framework:
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Transcriptomic: RNA-seq of adipose tissue macrophages (ATMs) post-treatment (focus: NLRP3/IL-1β pathways)
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Metabolomic: LC-MS quantification of palmitate/oleate ratios in hepatocytes
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Cellular: Bone marrow chimeras to isolate hematopoietic vs. parenchymal GLP-1R effects
Statistical rigor: Use linear mixed models to account for inter-animal variability in drug absorption (CV = 22–35%) .
