Exendin(9-39) amide acetate | CAS 2051593-46-3 | GLP-1 Receptor Antagonist for Postbariatric Hypoglycemia Research

Description

Product Description

Exendin(9-39) amide acetate is a synthetic peptide derived from the native exendin-4 sequence, designed as a selective glucagon-like peptide-1 (GLP-1) receptor antagonist. It competitively binds to GLP-1R, thereby inhibiting the effects of endogenous GLP-1, which is a key incretin hormone regulating insulin secretion and glucose homeostasis.

Originally developed to address hyperinsulinemic conditions such as postbariatric hypoglycemia (PBH), Exendin(9-39) amide acetate has become a critical tool in research exploring GLP-1 physiology, pancreatic beta-cell function, and glucose metabolism in both clinical and experimental models.

Molecular Features

Exendin(9-39) is a truncated derivative of exendin-4, lacking the first eight N-terminal amino acids, which are crucial for agonist activity. This truncation converts the peptide from a GLP-1R agonist to a competitive antagonist, capable of binding the receptor without activating downstream signaling. The acetate salt form improves stability and solubility for in vitro and in vivo applications.

Its amino acid sequence preserves receptor-binding affinity while abolishing insulinotropic activity, making it ideal for studying GLP-1R-specific effects independently of confounding agonist-mediated insulin release.

Biological Significance

GLP-1 is secreted by enteroendocrine L-cells in response to nutrient intake and plays a pivotal role in:

• Enhancing glucose-dependent insulin secretion

• Suppressing glucagon secretion

• Delaying gastric emptying

• Promoting satiety

Exendin(9-39) amide acetate selectively blocks these pathways, allowing researchers to delineate the physiological and pathophysiological roles of GLP-1, particularly in postbariatric patients who may experience exaggerated GLP-1 responses leading to hypoglycemia.

Applications in PBH Research

Postbariatric hypoglycemia is characterized by rapid glucose excursions and subsequent hyperinsulinemic hypoglycemia, primarily driven by excessive GLP-1 secretion after gastric bypass surgery. Exendin(9-39) amide acetate enables:

• Investigation of GLP-1-mediated insulin release kinetics

• Determination of beta-cell responsiveness under elevated incretin conditions

• Evaluation of therapeutic strategies that mitigate postprandial hypoglycemia

• Mechanistic studies on glucose homeostasis post-bariatric surgery

Metabolic Research Utility

Beyond PBH, Exendin(9-39) serves as a critical probe for:

• GLP-1 receptor-dependent insulinotropic and glucagonostatic pathways

• Pancreatic islet function and beta-cell signaling studies

• Nutrient-induced incretin regulation and enteroinsular axis modeling

• Therapeutic target validation for diabetes and metabolic disorders

Its precise receptor selectivity allows experimental separation of GLP-1R-mediated effects from other incretins or paracrine factors, providing clarity in complex metabolic studies.

Experimental Handling

Exendin(9-39) amide acetate is supplied as a lyophilized powder, soluble in water or PBS for cell culture and in vivo studies. Standard laboratory precautions apply:

• Avoid repeated freeze-thaw cycles

• Store at −20 °C, protected from light and moisture

• Prepare working solutions fresh to maintain bioactivity

Product Specifications

Mechanism of Action

Exendin(9-39) amide acetate functions primarily as a competitive GLP-1 receptor antagonist:

1. Competitive Receptor Binding

Exendin(9-39) binds to GLP-1R with high affinity but lacks the N-terminal residues required for receptor activation. This prevents endogenous GLP-1 from initiating downstream signaling, including:

• cAMP generation

• PKA activation

• Ca²⁺-dependent insulin exocytosis

2. Modulation of Beta-Cell Activity

By blocking GLP-1R, Exendin(9-39) reduces glucose-dependent insulin secretion, particularly in cells exposed to exaggerated GLP-1 levels post-bariatric surgery. This allows researchers to investigate intrinsic beta-cell function independently of GLP-1-mediated enhancement.

3. Glucagon and Glucose Regulation

GLP-1 normally suppresses glucagon secretion; Exendin(9-39) restores glucagon release in situations of excessive GLP-1, providing a model for studying counter-regulatory mechanisms in hypoglycemia.

4. Postbariatric Hypoglycemia Modeling

In PBH research, administration of Exendin(9-39) enables:

• Measurement of the difference in glucose and insulin excursions with and without GLP-1R inhibition

• Analysis of insulin secretory patterns in response to oral glucose or mixed meals

• Evaluation of therapeutic hyperglycemia-mitigating strategies

5. Integration in Metabolic Studies

Exendin(9-39) is used to clarify the contribution of GLP-1R in:

• Nutrient sensing

• Enteroinsular axis modulation

• Beta-cell proliferation and survival

• GLP-1-based incretin therapy responses

Its highly selective antagonism makes it an invaluable tool for dissecting GLP-1R-specific pathways in complex metabolic systems.

Side Effects

In experimental research, Exendin(9-39) exhibits predictable, low toxicity at standard concentrations. Observed effects include:

• Mild reduction in insulin secretion in glucose-challenged cells or animals

• Temporary hyperglycemia when administered in vivo under high GLP-1 conditions

• No mutagenic or genotoxic effects in standard laboratory assays

Exendin(9-39) is not intended for human or veterinary use; all experiments should follow biosafety protocols for peptide handling.

Keywords

Exendin(9-39) amide acetate, Avexitide, GLP-1 receptor antagonist, postbariatric hypoglycemia research, beta-cell modulation, metabolic regulation, glucose homeostasis, incretin signaling, GLP-1R inhibition, hyperinsulinemia model

Shipping Guarantee

All shipments are handled using validated cold-chain logistics to preserve peptide integrity. Each package is sealed in moisture-proof containers with secondary protective wrapping and continuous temperature monitoring. Products are shipped via express international couriers with full tracking and insurance coverage.

Trade Assurance

We ensure Exendin(9-39) amide acetate product authenticity, verified ≥99% purity, and compliance with analytical standards (HPLC, MS, and NMR). Each batch is supplied with a Certificate of Analysis (CoA). Our trade assurance policy guarantees replacement or refund for any deviation from listed specifications.

Payment Support

We provide flexible and secure global payment options to support international research transactions. Accepted payment methods include PayPal, major credit cards (Visa, MasterCard, American Express), telegraphic transfer (T/T), and cryptocurrencies (USDT, Bitcoin, Ethereum). All transactions are protected by industry-standard encryption and verified payment gateways to ensure confidentiality and fund security.

Disclaimer

Exendin(9-39) amide acetate products listed are intended for laboratory research use only and not for human or veterinary use. They are not drugs, medical devices, or diagnostics and should not be administered to humans or animals. Researchers must handle all materials in accordance with institutional biosafety and chemical safety guidelines. The information provided is for scientific reference only and does not imply therapeutic efficacy, safety, or regulatory approval.