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| Targets |
GIP receptor (GIPR). GIP, human is an endogenous peptide agonist of the GIP receptor (GIPR), a class B G protein-coupled receptor expressed on pancreatic beta-cells, adipocytes, bone, and in the central nervous system. Upon binding to GIPR, GIP activates Gs protein, leading to adenylate cyclase activation and increased intracellular cAMP. This signaling pathway enhances glucose-dependent insulin secretion from beta-cells, promoting glucose uptake and disposal. In adipocytes, GIP promotes fatty acid synthesis and lipid deposition, contributing to postprandial fat storage. GIP also inhibits gastric acid secretion, gastric emptying, and has effects on bone metabolism and satiety. The TFA salt is used to improve peptide stability and handling for research.
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| ln Vitro |
In the postprandial state, there is an increase in lipid deposition due to the many peripheral effects of Gastric Inhibitory Polypeptide (GIP) on lipid metabolism and adipose tissue [1]. GIP, lipid metabolism and the onset of obesity are major human factors.
In vitro, GIP, human TFA stimulates glucose-dependent insulin secretion from pancreatic beta-cell lines (e.g., INS-1, MIN6) and isolated human or rodent islets. At sub-threshold glucose concentrations (2.8-5 mM), GIP enhances GSIS (glucose-stimulated insulin secretion) in a concentration-dependent manner (EC50 0.1-1 nM). GIP also activates the cAMP/PKA pathway in adipocytes, promoting lipoprotein lipase activation and triglyceride synthesis. The peptide upregulates the expression of genes involved in adipogenesis (e.g., aP2, FAS). In cell lines expressing recombinant GIPR, GIP induces cAMP accumulation with high potency (EC50 ~0.1 nM). GIP also stimulates insulin gene transcription and beta-cell proliferation under certain conditions. The TFA counterion does not affect bioactivity. |
| ln Vivo |
In vivo, GIP, human TFA exerts its incretin effect, significantly augmenting insulin secretion following oral glucose administration. In animal models (rats, mice, dogs), intravenous or subcutaneous administration of GIP (10-100 ug/kg) prior to glucose challenge reduces blood glucose excursions. GIP promotes postprandial lipid storage by increasing chylomicron clearance and stimulating adipose tissue lipoprotein lipase activity. In perfused pancreas preparations, GIP enhances glucose-stimulated insulin secretion in a dose-dependent manner. GIP also weakly inhibits gastric acid secretion and slows gastric emptying, contributing to its overall metabolic effects. The TFA salt form is effective in vivo, though GIP is rapidly degraded by DPP-4 (half-life 2-5 minutes). Therefore, continuous infusion or DPP-4-resistant analogs are typically used for in vivo studies.
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| Enzyme Assay |
For radioligand binding assays, membranes prepared from CHO-K1 or HEK293 cells expressing human GIPR (10-50 ug protein/well) are incubated with 0.05-0.1 nM 125I-GIP 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 with or without unlabeled GIP (0.001-1000 nM). Bound and free radioligand are separated by rapid filtration through GF/C or GF/B glass fiber filters pre-soaked in 0.3% polyethyleneimine. Filters are washed, and radioactivity is counted. Specific binding is defined by subtracting non-specific binding (determined in the presence of 1 uM unlabeled GIP). IC50 values are calculated by nonlinear regression, and Ki is determined using the Cheng-Prusoff equation. For SPR, GIPR is immobilized on a sensor chip, and GIP is flowed over at varying concentrations (0.1-100 nM) to determine KD.
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| Cell Assay |
For cAMP accumulation assays, HEK293 or CHO-K1 cells stably expressing human GIPR are seeded in 96-well plates at 2 × 10^4 cells/well in culture medium (DMEM with 10% FBS) and grown for 24 hours. On the assay day, medium is replaced with serum-free DMEM containing 0.5 mM IBMX (phosphodiesterase inhibitor) and pre-incubated for 20 minutes at 37degC. Cells are then treated with GIP, human TFA at concentrations ranging from 0.001-1000 nM (10-fold serial dilutions) for 30 minutes at 37degC. After incubation, cells are lysed, and intracellular cAMP levels are measured using a homogeneous time-resolved fluorescence (HTRF) kit (Cisbio) or a chemiluminescence-based AlphaScreen kit. The EC50 is derived from a sigmoidal dose-response curve using a four-parameter logistic equation. For insulin secretion assays, INS-1 cells or isolated mouse islets are incubated with GIP (0.01-100 nM) plus 2.8 or 16.7 mM glucose for 1-2 hours, and secreted insulin is measured by ELISA.
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| Animal Protocol |
For in vivo studies, adult male Wistar rats (200-250 g) or C57BL/6J mice (8-10 weeks) are fasted for 6-16 hours. GIP, human TFA is dissolved in sterile saline (0.9% NaCl) or PBS at concentrations of 10-100 ug/mL. For intravenous administration, animals are anesthetized with isoflurane, and GIP is injected via the tail vein or jugular vein at doses of 1-100 ug/kg. For subcutaneous administration, GIP is injected into the scruff of the neck or lateral abdomen. For oral glucose tolerance tests (OGTT), GIP (5-50 ug/kg) is administered 10-15 minutes prior to oral glucose gavage (1-2 g/kg glucose solution). Blood glucose is measured from tail vein at -15, 0, 15, 30, 60, 90, 120 minutes post-glucose. Blood samples (50-100 uL) are collected into EDTA-coated tubes, centrifuged, and plasma insulin is measured by ELISA or RIA. For lipid metabolism studies, animals are administered GIP intravenously, and blood samples are collected for triglyceride, free fatty acid, and lipoprotein analysis. Tissue distribution studies are performed using 125I-labeled GIP.
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| ADME/Pharmacokinetics |
Native GIP is rapidly cleaved by the serine protease dipeptidyl peptidase-4 (DPP-4), which removes the two N-terminal amino acids (Tyr-Ala) to yield GIP(3-42), an inactive form. In humans and rodents, the plasma half-life of intact GIP is only 2-5 minutes following intravenous administration. DPP-4 inhibition (e.g., with sitagliptin) significantly increases plasma GIP levels and prolongs its activity. The peptide is cleared primarily by the kidneys (glomerular filtration) and undergoes limited hepatic metabolism. Due to its rapid clearance, continuous infusion (0.2-1 pmol/kg/min) is often used in in vivo studies to achieve steady-state plasma concentrations. The TFA salt (trifluoroacetate) is a common counterion in peptide research and does not alter the intrinsic pharmacokinetics of GIP. GIP(1-42) binds to albumin in plasma, which modestly reduces free fraction and clearance.
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| Toxicity/Toxicokinetics |
As an endogenous hormone, GIP is well-tolerated and has no significant toxicity at physiological concentrations (low picomolar to low nanomolar). In animal studies, supraphysiological doses (e.g., 100-1000 ug/kg) may cause transient hypotension, flushing, tachycardia, and mild gastrointestinal disturbances (nausea, diarrhea), which are consistent with activation of GIPR in the cardiovascular and digestive systems. No genotoxicity, organ toxicity, or carcinogenicity has been reported for GIP. The TFA salt is present in stoichiometric amounts (typically 1-2 equivalents) and is generally considered non-toxic at the quantities used in research (micromolar to millimolar concentrations in buffers). Chronic elevation of GIP levels (via DPP-4 inhibitors or GIP analogs) may contribute to adiposity and metabolic dysfunction in susceptible individuals, as GIP promotes lipid storage in adipose tissue.
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| References |
[1]. Meier JJ, et al. Gastric inhibitory polypeptide: the neglected incretin revisited. Regul Pept. 2002 Jul 15;107(1-3):1-13.
[2]. Miyachi A, et al. Quantitative analytical method for determining the levels of gastric inhibitory polypeptides GIP1-42 and GIP3-42 in human plasma using LC-MS/MS/MS. J Proteome Res. 2013;12(6):2690-2699. [3]. Gabe MBN, et al. Molecular interactions of full-length and truncated GIP peptides with the GIP receptor - A comprehensive review. Peptides. 2020;125:170224. |
| Additional Infomation |
Gastric inhibitory polypeptide (GIP) was initially named for its ability to inhibit gastric acid secretion, but it was later found to be more potent as an insulin secretagogue and was renamed glucose-dependent insulinotropic polypeptide (GIP). GIP is produced and secreted by intestinal K-cells (primarily in the duodenum and jejunum) in response to nutrient ingestion, especially fat and carbohydrates. GIP is one of two major incretin hormones, the other being GLP-1. Unlike GLP-1, GIP does not inhibit gastric emptying or suppress appetite to the same extent, and its effects on glucose metabolism are more modest. However, GIP acts as a key regulator of lipid metabolism, promoting triglyceride storage in adipose tissue. Human GIP(1-42) differs from rodent (rat, mouse) GIP by several amino acid substitutions, so human studies require the human peptide. The TFA salt is a common formulation for stabilizing peptides during lyophilization and storage. Native GIP(1-42) is not an approved drug, but GIPR agonists and dual GIPR/GLP-1R agonists (e.g., tirzepatide) are under development for type 2 diabetes and obesity. GIP, human TFA is for research use only.
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| Molecular Formula |
C228H339F3N60O68S
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| Molecular Weight |
5097.62
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| Related CAS # |
GIP, human;100040-31-1
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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 |
| 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) |
H2O :~10 mg/mL (~1.96 mM)
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.1962 mL | 0.9808 mL | 1.9617 mL | |
| 5 mM | 0.0392 mL | 0.1962 mL | 0.3923 mL | |
| 10 mM | 0.0196 mL | 0.0981 mL | 0.1962 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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