GLP-1 receptor[1].
GLP-1 receptor (GLP-1R). Glucagon-like peptide 1 (1-37), human is a full-length form of the incretin hormone GLP-1, consisting of 37 amino acids. It is produced by post-translational processing of proglucagon in intestinal L-cells. GLP-1(1-37) can activate the GLP-1 receptor (GLP-1R), a class B G protein-coupled receptor. Upon binding to GLP-1R, it activates Gs protein, leading to increased intracellular cAMP, which enhances glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells, suppresses glucagon release, slows gastric emptying, and promotes satiety. Although GLP-1(1-37) is the precursor form, it retains full agonist activity at GLP-1R. It is actually more stable in serum compared to GLP-1(7-37) because the N-terminal extension (His1-Asp-Glu-Phe-Glu-Arg-His) may protect against dipeptidyl peptidase-4 (DPP-4) cleavage, although DPP-4 still can cleave after Ala8 (GLP-1(1-37) has a different N-terminus, but the DPP-4 cleavage site may be absent or altered). Studies show that GLP-1(1-37) is a highly potent GLP-1R agonist. The TFA salt is used for peptide stabilization. This product is for research use only.

Glucagon-like peptide-1(GLP-1) is generated through the posttranslational processing of proglucagon and functions as a modulator of multiple homeostatic processes. After being exposed to mouse serum for 4 hours, GLP-1(1-37) retains 94.7% of its initial peptide content, making it more stable than GLP-1(7-37). By assessing the luciferase reporter gene expression in transiently transfected human embryonic kidney (HEK293) cells, GLP-1(1-37) is verified as a highly powerful agonist of the GLP-1 receptor (GLP-1R)[1].

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In vitro, Glucagon-like peptide 1 (1-37), human TFA is a potent agonist of the GLP-1 receptor. In HEK293 cells transiently transfected with the GLP-1R plasmid and a CRE-luciferase reporter plasmid, treatment with GLP-1(1-37) or GLP-1(7-37) for 5 hours induces luciferase expression in a concentration-dependent manner. The EC50 of GLP-1(1-37) is comparable to that of GLP-1(7-37) (low nanomolar range, e.g., 0.1-1 nM). In cAMP accumulation assays, GLP-1(1-37) (0.01-100 nM) stimulates cAMP production in GLP-1R-expressing cells. It also stimulates glucose-dependent insulin secretion in isolated rodent and human pancreatic islets (EC50 ~0.1-1 nM). The full-length peptide is more stable in serum compared to GLP-1(7-37): after 4-hour incubation in mouse serum at 37degC, 94.7% of GLP-1(1-37) remains intact, whereas GLP-1(7-37) is extensively degraded. This increased stability may be due to the protective effect of the N-terminal extension. In insulinoma cell lines (e.g., INS-1, MIN6), GLP-1(1-37) promotes cell proliferation and protects against apoptosis induced by cytokines or endoplasmic reticulum stress. The TFA counterion does not affect biological activity. The peptide sequence is: His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (C-terminal free acid).

GLP-1(1-37) has a dose-dependent reduction in hyperglycemia excursion. When compared to the control group, the injection of GLP-1(1-37) or GLP-1(7–37) significantly lowers blood glucose levels at 15 and 30 minutes[1].

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In vivo, Glucagon-like peptide 1 (1-37), human TFA decreases glycemic excursion in a dose-dependent manner. In studies using normal KM mice, administration of GLP-1(1-37) (25 nmol/kg) or GLP-1(7-37) (25 nmol/kg) markedly decreases blood glucose levels at 15 min and 30 min compared to control group, in conjunction with intraperitoneal glucose injection (4 g/kg). The glucose-lowering effect of GLP-1(1-37) is blocked by exendin(9-39) (250 nmol/kg), a GLP-1R antagonist, confirming that the effect is GLP-1R-mediated. In diabetic animal models (e.g., db/db mice, STZ-induced diabetic rats), intraperitoneal or subcutaneous administration of GLP-1(1-37) (10-100 nmol/kg) reduces fasting and postprandial blood glucose, and improves glucose tolerance. The full-length peptide may have a longer duration of action than GLP-1(7-37) due to its increased stability. However, its plasma half-life is still short (minutes) compared to DPP-4-resistant GLP-1 analogs. The peptide is not used therapeutically; it is a research tool. The TFA salt is suitable for in vivo injection (dissolve in PBS or saline). No chronic efficacy studies have been reported, and it is not an approved drug.

For non-cellular receptor binding assays, a competitive radioligand binding assay can be performed using membranes from GLP-1R-expressing cells (e.g., HEK293-GLP-1R) and a radiolabeled GLP-1 analog (e.g., 125I-GLP-1(7-36) amide). Membranes (20-50 ug protein/well) are incubated with 0.05-0.1 nM 125I-GLP-1 and varying concentrations of unlabeled GLP-1(1-37) TFA (0.001-1000 nM) in binding buffer (50 mM HEPES pH 7.4, 1 mM CaCl2, 5 mM MgCl2, 0.5% BSA, 0.1% bacitracin) for 60-90 minutes at 25degC. Bound and free radioligand are separated by filtration through GF/B filters pre-soaked in 0.3% polyethyleneimine, and radioactivity is counted. IC50 is determined, and Ki is calculated. The Ki should be in the low nanomolar range (0.1-10 nM). For a direct binding assay using SPR, the GLP-1R protein can be immobilized on a sensor chip, and GLP-1(1-37) is flowed over at concentrations 0.1-100 nM. Association and dissociation are recorded, and KD is calculated. This assay may require stabilization of the class B GPCR in an active state. Alternatively, a homogeneous time-resolved fluorescence (HTRF) binding assay using a fluorescently labeled GLP-1 can be performed. These protocols are for reference; the compound is typically used in cell-based functional assays. The TFA salt is water-soluble.

For cellular functional assays (cAMP accumulation), HEK293 cells stably expressing human GLP-1R are seeded in 96-well plates (2-4 × 10^4 cells/well) in DMEM with 10% FBS. After 24 h, cells are washed with PBS, and the medium is replaced with serum-free DMEM containing 0.5 mM IBMX (phosphodiesterase inhibitor). Cells are pre-incubated for 20 min at 37degC. Then, varying concentrations of GLP-1(1-37) TFA (0.001-1000 nM) are added and incubated for 30 min at 37degC. Cells are lysed, and intracellular cAMP levels are measured using an HTRF cAMP kit (Cisbio) or a chemiluminescence-based AlphaScreen kit. The EC50 is determined by nonlinear regression (four-parameter logistic fit). Typically, the EC50 is 0.1-1 nM. For CRE-luciferase reporter assays: HEK293 cells are co-transfected with GLP-1R plasmid and a CRE-luciferase reporter plasmid (containing cAMP response elements). After 24-48 h, cells are treated with GLP-1(1-37) (0.001-1000 nM) for 5 hours. Luciferase activity is measured using a luciferase assay kit. The EC50 is similar. For insulin secretion assays: INS-1 cells (or isolated mouse islets) are seeded in 96-well plates and starved in low-glucose (2.8 mM) KRB buffer for 1-2 h. Cells are then incubated with GLP-1(1-37) (0.01-100 nM) in KRB buffer containing 2.8 or 16.7 mM glucose for 1 h at 37degC. Supernatants are collected, and insulin is measured by ELISA. GLP-1(1-37) enhances insulin secretion only at high glucose (16.7 mM). The peptide is not cytotoxic at concentrations up to 1000 nM. For stability assays in serum: GLP-1(1-37) TFA (1 uM) is incubated in mouse, rat, or human serum at 37degC for 0, 1, 2, 4, 8, 24 h. The reaction is terminated by adding acetonitrile (3:1) containing an internal standard (e.g., a stable isotope-labeled GLP-1), and the remaining intact peptide is quantified by LC-MS/MS. Percent remaining is calculated. GLP-1(1-37) is expected to be more stable than GLP-1(7-37). All experiments should be performed in triplicate with at least 3 independent experiments. Stock solution: Dissolve peptide in water or 10 mM acetic acid (1-10 mM), store at -80degC in small aliquots. Avoid freeze-thaw cycles. The TFA salt is stable. Dilute in assay buffer containing 0.1% BSA to prevent adsorption.

For in vivo studies, normal KM mice (or C57BL/6J mice, 8-10 weeks old) are fasted for 16 hours. GLP-1(1-37) TFA is dissolved in sterile saline or PBS. The peptide is administered intraperitoneally (i.p.) at doses of 10-100 nmol/kg (e.g., 25 nmol/kg). A positive control group receives GLP-1(7-37) (25 nmol/kg). A negative control group receives vehicle (saline). After 10-15 minutes, an intraperitoneal glucose tolerance test (IPGTT) is performed: glucose (4 g/kg) is injected i.p., and blood glucose levels are measured from tail vein at 0 (pre-glucose), 15, 30, 60, 90, 120 minutes using a glucometer. To confirm GLP-1R mediation, a separate group receives exendin(9-39) (250 nmol/kg, i.p.) 5 minutes before GLP-1(1-37). Blood glucose levels are recorded. The glucose-lowering effect is expressed as the reduction in blood glucose area under the curve (AUC) relative to vehicle. For diabetic models (db/db mice or STZ-induced diabetic mice), repeated dosing (once daily for 2-4 weeks) may be performed, but published data are limited. At the end of the study, blood may be collected for insulin ELISA. The TFA salt is suitable for in vivo use; adjust pH to 7.4 if necessary. The peptide is well-tolerated at these doses, with no observed adverse effects (e.g., hypoglycemia, nausea, vomiting). All animal procedures require IACUC approval. The peptide is not an approved drug; it is for research use only.

The pharmacokinetics (PK) of GLP-1(1-37) have not been extensively characterized. In mice, after intraperitoneal administration, GLP-1(1-37) has a relatively short plasma half-life (estimated 2-10 minutes) due to renal clearance (glomerular filtration) and proteolytic degradation. However, it is reported to be more stable than GLP-1(7-37) in serum: 94.7% remains intact after 4 hours in mouse serum, compared to rapid degradation of GLP-1(7-37). This suggests that the N-terminal extension (residues 1-6) protects against cleavage by DPP-4 and other peptidases. The peptide is cleared by the kidneys and metabolized by neutral endopeptidases (NEP) and other proteases. The TFA salt does not affect PK. For a PK study: Mice receive GLP-1(1-37) TFA (25 nmol/kg, i.p.). Blood is collected at 0, 5, 10, 20, 30, 60, 90, 120 min. Plasma is treated with a DPP-4 inhibitor and protease inhibitors immediately after collection to prevent ex vivo degradation. GLP-1(1-37) concentration is measured by a specific ELISA or by LC-MS/MS. PK parameters (Cmax, Tmax, AUC, t1/2) are calculated. The absolute bioavailability after oral administration is negligible (<1%). The compound is not a drug, so PK data are not widely reported. For research use only, not for clinical development.

No specific toxicity data are available for GLP-1(1-37), human TFA. As a full-length endogenous peptide hormone, GLP-1(1-37) is generally considered to have low toxicity. In animal studies, acute administration of GLP-1(1-37) at doses up to 100 nmol/kg (approximately 400 ug/kg) i.p. does not cause overt signs of toxicity (e.g., death, seizures, abnormal behavior) in mice. The compound is not cytotoxic in cell cultures at concentrations up to 1 uM. No genotoxicity, carcinogenicity, or reproductive toxicity studies have been conducted. The TFA salt (trifluoroacetate) is present in stoichiometric amounts (typically 1:1 ratio with the peptide) and is generally considered non-toxic at the doses administered. The peptide is not an approved drug; it is for research use only. Standard laboratory safety precautions (gloves, lab coat) should be used. This product is not intended for human use.

[1]. Zhao L, et al. Glucagon-like peptide-1(1-37) can enhance blood glucose homeostasis in mice. Regul Pept. 2012 Oct 10;178(1-3):1-5.

GLP-1 (glucagon-like peptide-1) is derived from the proglucagon gene. Proglucagon is processed in a tissue-specific manner: in the pancreas, it is processed to glucagon; in the intestine, it is processed to glicentin, GLP-1, and GLP-2. The major active forms of GLP-1 are GLP-1(7-36) amide and GLP-1(7-37). GLP-1(1-37) is the immediate precursor of these active peptides and has been shown to have biological activity at the GLP-1 receptor. Historically, it was believed that GLP-1(1-37) was inactive, but later studies demonstrated that it is a full agonist, albeit with lower potency than the truncated forms in some assays. It is also more stable in serum than GLP-1(7-37), making it a useful research tool for studying GLP-1 biology without rapid degradation. The TFA salt is used for improved solubility and stability. GLP-1(1-37) is not an approved drug; it is for research use only. The product is not intended for human therapy. It is typically used in studies of GLP-1 production, processing, and receptor activation.

C188H276N51F3O61

4283.50

Glucagon-like peptide 1 (1-37), human;87805-34-3

Typically exists as solid at room temperature

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)