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| Targets |
GLP-1 receptor (GLP-1R). GLP-1(7-36), amide binds with high affinity to the GLP-1 receptor, a class B G protein-coupled receptor (GPCR) predominantly expressed on pancreatic beta-cells, but also found in the brain, heart, kidney, stomach, and other tissues. Upon agonist binding, the receptor activates Gs protein, increasing intracellular cAMP levels and subsequently activating cAMP-dependent protein kinase (PKA) and Epac2. This signaling pathway leads to enhanced glucose-dependent insulin gene transcription, increased insulin biosynthesis, and potentiation of glucose-stimulated insulin secretion (GSIS), as well as promotion of beta-cell proliferation and survival.
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| ln Vitro |
The quantities of active GLP-1(7-36) Acetate (Human GLP-1-(7-36)-amide Acetate) in the medium were considerably greater in the cells treated with phorbol 12-myristate 13-acetate for two hours compared to the control group. Additionally, in a dose-dependent manner, the glucose administration raises the active GLP-1 release from cells. Active GLP-1 secretion from cells was dose-dependently enhanced by palmitic, oleic, linoleic, or linolenic acid. Compared to palmitic acid, unsaturated fatty acids including oleic, linoleic, and linolenic acids considerably increase active GLP-1 production. Active GLP-1 concentrations in the medium are dose-dependently increased when NCI-H716 cells are treated with CPE. At a concentration of 0.1% CPE, there is a 37% increase in these cells' active GLP-1 secretion[1].
In vitro, GLP-1(7-36), amide induces glucose-stimulated insulin secretion from isolated pancreatic beta-cells and islet preparations. Cells treated with phorbol 12-myristate 13-acetate (PMA) for 2 hours show significantly higher concentrations of active GLP-1(7-36) amide in the culture media compared to control. The peptide promotes beta-cell proliferation and protects against apoptosis induced by various stressors. At the molecular level, GLP-1(7-36), amide activates the PKA and PI3K pathways, leading to PDX-1 nuclear translocation and increased expression of insulin and other beta-cell-specific genes. It also enhances glucose uptake and glycogen synthesis in peripheral tissues. |
| ln Vivo |
Active GLP-1(7-36) amide levels in the portal blood rise following gastric glucose delivery after 10 minutes, and then they sharply decline after 30 minutes. After 10 minutes, the stomach delivery of TO also raises active GLP-1 levels, which subsequently drop to basal levels after 60 minutes. The secretion of GLP-1 is dose-dependently increased by glucose and TO alone. Moreover, peak GLP-1 levels are additively increased by the simultaneous administration of glucose and TO. Within the portal blood at 10 and 30 minutes, mice given CPE had elevated amounts of active GLP-1 compared to the control group. When CPE is given in addition to glucose, the mice receiving CPE have somewhat higher levels of insulin and active GLP-1 in their portal blood than the mice receiving no CPE. C57BL/6J mice fed a high-fat diet experience glucose intolerance impairment and hyperglycemia [1].
In vivo, GLP-1(7-36), amide potently lowers blood glucose levels in a glucose-dependent manner. Intravenous or subcutaneous administration in animal models of type 2 diabetes reduces fasting and postprandial glucose excursions. The peptide slows gastric emptying, reduces food intake via central mechanisms, and suppresses inappropriate glucagon secretion. In diabetic rodents, chronic GLP-1(7-36), amide infusion improves beta-cell function and enhances insulin sensitivity. However, its therapeutic utility is limited by rapid degradation by dipeptidyl peptidase-4 (DPP-4), resulting in a very short plasma half-life of approximately 1-2 minutes. |
| Enzyme Assay |
For direct binding assays, the GLP-1 receptor (human recombinant) is immobilized onto sensor chips for surface plasmon resonance (SPR). Varying concentrations of GLP-1(7-36), amide TFA (0-1000 nM) are flowed over the surface to measure binding affinity (KD). Alternatively, competitive radioligand binding assays using 125I-labeled GLP-1(7-36) amide and HEK293 cell membranes expressing human GLP-1R can be performed. After incubation at room temperature for 60-120 minutes, bound and free radioligands are separated by rapid filtration through glass fiber filters. Radioactivity is quantified by gamma counting to determine specific binding and IC50 values.
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| Cell Assay |
INS-1E cells, RINm5F cells, or isolated primary mouse islets are seeded in 96-well plates in RPMI-1640 containing 10% FBS and 11 mM glucose. After overnight recovery, cells are starved in low-glucose (2.8 mM) medium for 2 hours, then treated with GLP-1(7-36), amide TFA (0-100 nM) in Krebs-Ringer bicarbonate buffer (KRB) containing 2.8 or 16.7 mM glucose for 1-2 hours at 37degC. Supernatants are collected for insulin measurement by ELISA or HTRF. Intracellular cAMP levels are quantified using a cAMP homogeneous time-resolved fluorescence (HTRF) or chemiluminescence-based assay kit. Live-cell imaging of calcium flux using Fluo-4 AM can assess real-time beta-cell activation.
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| Animal Protocol |
Male C57BL/6J mice or db/db diabetic mice are fasted overnight and then subjected to an intraperitoneal glucose tolerance test (IPGTT). GLP-1(7-36), amide TFA (10-100 ug/kg) or vehicle is administered subcutaneously or intravenously 15 minutes before glucose challenge (1-2 g/kg). Blood glucose levels are measured at 0, 15, 30, 60, 90, and 120 minutes post-glucose using a glucometer. For insulin secretion studies, blood samples are collected from the tail vein at multiple time points, and plasma insulin is quantified by ELISA. For gastric emptying assessment, mice are gavaged with a non-absorbable dye, and gastric retention is measured after 15 minutes.
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| ADME/Pharmacokinetics |
GLP-1(7-36), amide is rapidly cleaved by the serine protease DPP-4 at the Ala2-Glu3 bond, yielding the metabolite GLP-1(9-36) amide, which lacks insulinotropic activity. In humans and rodents, the plasma half-life is only 1-2 minutes. The peptide is primarily cleared by the kidneys and also undergoes degradation by neutral endopeptidase 24.11 (NEP). Due to its rapid clearance, continuous intravenous infusion or administration of DPP-4-resistant GLP-1 analogs is required to achieve therapeutic exposure. Subcutaneous bioavailability is low because of rapid enzymatic degradation. The TFA salt form does not alter the intrinsic pharmacokinetic properties of the native peptide.
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| Toxicity/Toxicokinetics |
GLP-1(7-36), amide is an endogenous peptide hormone with no significant toxicity at physiological concentrations. In animal studies, suprapharmacological doses (above 1 mg/kg) may cause transient nausea, vomiting (in emetic species), and mild hypotension, consistent with its known pharmacological effects. No genotoxicity, organ toxicity, or immunogenicity has been reported. DPP-4-resistant GLP-1 analogs (e.g., exenatide, liraglutide) used in clinical practice have been associated with gastrointestinal side effects and rare cases of pancreatitis in humans, but these are not observed with the native peptide in research settings. The TFA counterion is present in small amounts and is generally considered non-toxic.
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| References |
[1]. Fujii Y et al. Ingestion of coffee polyphenols increases postprandial release of the active glucagon-like peptide-1(GLP-1(7-36)) amide in C57BL/6J mice. J Nutr Sci. 2015 Mar 3;4:e9.
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| Additional Infomation |
GLP-1(7-36), amide (human GLP-1) is the natural incretin hormone responsible for the "incretin effect" - the augmentation of insulin secretion after oral glucose intake compared to intravenous glucose. The peptide is synthesized as proglucagon in intestinal L-cells and processed by prohormone convertase 1/3 to yield GLP-1(1-37) and GLP-1(7-36) amide, with the C-terminal amidated form being the predominant bioactive species. Several GLP-1 receptor agonists (exenatide, liraglutide, dulaglutide, semaglutide) have been approved for type 2 diabetes and obesity, but native GLP-1(7-36), amide itself is not an approved drug. The TFA salt form is used exclusively for research purposes.
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| Molecular Formula |
C151H227F3N40O47
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| Molecular Weight |
3411.65
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| Related CAS # |
GLP-1(7-36), amide acetate;1119517-19-9;GLP-1(7-36), amide;107444-51-9
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| Appearance |
Typically exists as solid at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
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. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :≥ 50 mg/mL (~14.66 mM)
H2O :< 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (0.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (0.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (0.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2931 mL | 1.4656 mL | 2.9311 mL | |
| 5 mM | 0.0586 mL | 0.2931 mL | 0.5862 mL | |
| 10 mM | 0.0293 mL | 0.1466 mL | 0.2931 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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