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| 10mg |
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| Targets |
GIP receptor (GIPR). GIP (1-30) amide is a full agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR), a class B G protein-coupled receptor. The peptide binds to GIPR with an affinity comparable to that of the full-length native GIP(1-42). Activation of GIPR by GIP (1-30) amide stimulates downstream Gs protein-mediated signaling, resulting in increased adenylate cyclase activity and elevated intracellular cAMP levels. This leads to potentiation of glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells. The shortened 1-30 fragment retains the pharmacophore and key binding determinants of the full-length peptide, making it an effective and high-affinity agonist for research purposes.
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| ln Vitro |
In vitro, GIP (1-30) amide is a full agonist of the GIP receptor, with potency comparable to that of native GIP(1-42). The compound induces cAMP accumulation in GIPR-expressing cell lines with an EC50 in the low nanomolar range (typically 0.1-1 nM). In isolated pancreatic islets or beta-cell lines (INS-1, MIN6), GIP (1-30) amide (0.01-100 nM) potentiates glucose-stimulated insulin secretion (GSIS) at stimulatory glucose concentrations (8-20 mM) but not at basal glucose (2.8-5 mM), maintaining the glucose-dependency that is a hallmark of incretin action. GIP (1-30) amide is also a weak inhibitor of gastric acid secretion in cellular models. The C-terminal amidation increases stability against carboxypeptidase-mediated degradation compared to the free acid form.
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| ln Vivo |
In vivo, GIP (1-30) amide acts as a weak inhibitor of gastric acid secretion and a potent stimulator of insulin secretion. In animal models (rats, mice, pigs), intravenous or subcutaneous administration of GIP (1-30) amide (1-100 ug/kg) prior to oral or intraperitoneal glucose challenge enhances glucose-stimulated insulin secretion and reduces blood glucose excursions in a glucose-dependent manner. The compound stimulates insulin secretion without causing hypoglycemia at euglycemic levels. Compared to full-length GIP(1-42), GIP(1-30) amide has similar insulinotropic efficacy but reduced gastric acid inhibitory effects, making it a useful tool to dissociate the two biological activities. The truncated peptide may have slightly improved stability against some proteases relative to GIP(1-42), though it remains susceptible to DPP-4 cleavage (which removes the N-terminal dipeptide).
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| Enzyme Assay |
For in vitro binding assays, a competitive radioligand binding assay can be performed. Membranes from CHO-K1 or HEK293 cells expressing the porcine or human GIP receptor are prepared by homogenization in binding buffer (25 mM Tris-HCl pH 7.4, 1 mM CaCl2, 5 mM MgCl2, 0.2% BSA, 0.1% bacitracin). Membranes (10-50 ug protein/well) are incubated in 96-well plates with 0.05-0.1 nM 125I-GIP(1-42) (or 125I-GIP(1-30) amide) and varying concentrations of unlabeled GIP (1-30) amide (0.01-1000 nM) for 90 minutes at 25degC with gentle shaking. Bound and free radioligand are separated by rapid filtration through GF/B glass fiber filters pre-soaked in 0.3% PEI. Filters are washed with cold binding buffer, and bound radioactivity is quantified. Non-specific binding is determined in the presence of 1 uM unlabeled GIP(1-42). IC50 values are converted to Ki using the Cheng-Prusoff equation. Affinity is determined to be comparable to GIP(1-42).
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| Cell Assay |
For cellular functional assays, HEK293 or CHO-K1 cells stably expressing the GIP receptor are seeded in 96-well plates at 2-5 × 10^4 cells/well in DMEM containing 10% FBS and incubated for 24 hours at 37degC, 5% CO2. On the day of the assay, medium is replaced with serum-free DMEM containing 0.5 mM IBMX (phosphodiesterase inhibitor) and incubated for 20 minutes at 37degC. GIP (1-30) amide is serially diluted (10-fold, 0.1 pM to 1 uM) in assay buffer (HBSS with 0.1% BSA and 0.5 mM IBMX) and added to cells. After 30 minutes of incubation at 37degC, cells are lysed, and intracellular cAMP is quantified using an HTRF cAMP kit (Cisbio) or AlphaScreen cAMP detection kit. The EC50 is derived from a sigmoidal dose-response curve using a four-parameter logistic model. For insulin secretion studies, isolated mouse islets or INS-1 832/13 beta-cells are seeded in 24-well plates and pre-incubated in KRB buffer (2.8 mM glucose) for 1 hour. Then, islets/cells are incubated with GIP (1-30) amide (0.1-100 nM) in KRB buffer containing 2.8 or 16.7 mM glucose for 1 hour at 37degC. Supernatants are collected, and insulin is measured by ELISA (e.g., Mercodia, ALPCO). GIP(1-30) amide should enhance insulin secretion only at high glucose concentrations.
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| Animal Protocol |
For in vivo pharmacodynamic studies, adult male Wistar rats (200-300 g) or C57BL/6J mice (8-12 weeks) are fasted for 6-16 hours prior to experiments. GIP (1-30) amide is dissolved in sterile 0.9% saline or PBS at concentrations of 10-100 ug/mL and administered intravenously (via tail vein) or subcutaneously at doses of 5-100 ug/kg. For OGTT, GIP (1-30) amide or vehicle is injected 10-15 minutes prior to oral glucose administration (1-2 g/kg glucose solution given by gavage). Blood glucose is measured from tail vein using a glucometer at -15 (pre-treatment), 0 (immediately pre-glucose), and 15, 30, 60, 90, 120 minutes after glucose. Blood samples (50-100 uL) are collected into chilled EDTA-coated tubes, plasma separated by centrifugation (2,000 g, 10 min, 4degC), and stored at -80degC for insulin measurement by ELISA. For gastric acid secretion studies, pylorus-ligated rats are used: after laparotomy, the pylorus is ligated, and GIP (1-30) amide (1-100 ug/kg) is administered intravenously. After 2-4 hours, gastric contents are collected, volume measured, and acid content determined by titration with 0.1 N NaOH. GIP(1-30) amide should produce weak inhibition of gastric acid secretion compared to GIP(1-42).
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data are available for GIP (1-30) amide. As a truncated analog of the native incretin hormone GIP(1-42), it is expected to be rapidly cleared in vivo. The peptide is susceptible to degradation by DPP-4 (dipeptidyl peptidase-4), which cleaves after the N-terminal Tyr-Ala dipeptide, generating inactive GIP(3-30) amide. The plasma half-life of GIP(1-30) amide in rodents is likely less than 5-10 minutes following intravenous administration. The C-terminal amidation does not protect against DPP-4-mediated N-terminal cleavage but may improve stability against C-terminal degradation. The TFA salt form does not alter the pharmacokinetic profile. For experiments requiring sustained exposure, continuous infusion via osmotic minipump or co-administration with a DPP-4 inhibitor (e.g., sitagliptin, vildagliptin) may be employed. Clearance occurs primarily via renal filtration and enzymatic degradation.
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| Toxicity/Toxicokinetics |
No specific toxicity data are available for GIP (1-30) amide, porcine TFA. As a fragment of an endogenous peptide hormone, GIP(1-30) amide is expected to have low toxicity at standard research doses (ug/kg to mg/kg). In animal studies, suprapharmacological doses (e.g., >100 ug/kg) may cause transient, mild adverse effects consistent with GIPR activation, including gastrointestinal disturbances (nausea, diarrhea, abdominal discomfort), flushing, and mild hypotension due to vasodilation. However, such effects are not well-characterized for the truncated analog. No genotoxicity, organ toxicity, or carcinogenicity has been reported. The TFA counterion is present in low, stoichiometric amounts and is generally considered non-toxic. GIP(1-30) amide is for research use only and not intended for human or therapeutic applications. GIP (1-30) amide is a shortened, C-terminally amidated analog of full-length GIP(1-42) derived from porcine sequence (which differs from human GIP by a few amino acids). Native porcine GIP(1-42) is 42 amino acids in length, and the 1-30 fragment contains the N-terminal region that harbors the pharmacophore necessary for receptor activation and insulinotropic activity. The C-terminal amidation is a common modification to enhance peptide stability and bioactivity. This truncated analog has comparable potency to GIP(1-42) in stimulating insulin secretion but reduced ability to inhibit gastric acid secretion, making it useful for structure-activity relationship (SAR) studies of the GIP receptor and for dissecting the biological functions of the parent hormone. The TFA salt is used for improved peptide handling and stability in research applications. GIP (1-30) amide is for research use only; it is not an approved drug.
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| References |
| Molecular Formula |
C164H246F3N41O49S
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| Molecular Weight |
3665.02
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| Related CAS # |
GIP (1-30) amide, porcine;134846-93-8
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| Appearance |
Solid powder
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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 :~100 mg/mL (~27.28 mM)
H2O :< 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (0.68 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (0.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2728 mL | 1.3642 mL | 2.7285 mL | |
| 5 mM | 0.0546 mL | 0.2728 mL | 0.5457 mL | |
| 10 mM | 0.0273 mL | 0.1364 mL | 0.2728 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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