[Pro3]-GIP (Mouse)
目录号 : GC50278
[Pro3]-GIP (Mouse)是一种高效的酶抵抗型gastric inhibitory polypeptide (GIP)受体拮抗剂，IC50值为2.6μM。
![[Pro3]-GIP (Mouse) Chemical Structure](/media/struct/GC5/GC50278.png "[Pro3]-GIP (Mouse) Chemical Structure")
Sample solution is provided at 25 µL, 10mM.
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[Pro3]-GIP (Mouse) is potent enzyme-resistant gastric inhibitory polypeptide (GIP) receptor antagonist, with an IC50 value of 2.6μM[1]. [Pro3]-GIP can block the ability of native GIP to increase cAMP and stimulate insulin secretion[2]. [Pro3]-GIP has been widely used in diabetes mouse and obesity mouse models to improve the obesity phenotype and β-cell function[3].
In vitro, [Pro3]-GIP treatment at 1μM for 10min significantly inhibited cAMP generation in GIP receptor-transfected CHL cells[4]. Treatment of BRIN-BD11 cells with 1μM [Pro3]-GIP for 20 minutes significantly inhibited the release of insulin induced by natural GIP (0.1μM)[5].
In vivo, [Pro3]-GIP treatment via intraperitoneally injection at a dose of 25nmol/kg/day for 60 days significantly improved non-fasting glucose and insulin sensitivity in ob/ob mice[6]. Continuous intraperitoneal injection of 25nmol/kg/day dose of [Pro3]-GIP for 20 consecutive days aggravated hyperglycemia and glycosylated hemoglobin in the streptozotocin-induced diabetic mouse model, reduced glucose tolerance, and impaired insulin sensitivity[7]. [Pro3]-GIP (25nmol/kg/day) combined with AM251 (6mg/kg/day) was administered intraperitoneally for 22 consecutive days, which reduced the blood glucose levels and glucose tolerance in high-fat-fed mice and decreased the body weight[8].
References:
[1] Gault V A, O'Harte F P M, Harriott P, et al. Characterization of the cellular and metabolic effects of a novel enzyme-resistant antagonist of glucose-dependent insulinotropic polypeptide[J]. Biochemical and biophysical research communications, 2002, 290(5): 1420-1426.
[2] Koefoed-Hansen F, Helsted M M, Kizilkaya H S, et al. The evolution of the therapeutic concept ‘GIP receptor antagonism’[J]. Frontiers in Endocrinology, 2025, 16: 1570603.
[3] Gault V A, Irwin N, Green B D, et al. Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3) GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes[J]. Diabetes, 2005, 54(8): 2436-2446.
[4] Gault V A, O'harte F P M, Harriott P, et al. Effects of the novel (Pro3) GIP antagonist and exendin (9–39) amide on GIP-and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin[J]. Diabetologia, 2003, 46(2): 222-230.
[5] McClean P L, Irwin N, Hunter K, et al. (Pro3) GIP [mPEG]: novel, long‐acting, mPEGylated antagonist of gastric inhibitory polypeptide for obesity‐diabetes (diabesity) therapy[J]. British journal of pharmacology, 2008, 155(5): 690-701.
[6] Irwin N, McClean P L, O’harte F P M, et al. Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3) GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice[J]. Diabetologia, 2007, 50(7): 1532-1540.
[7] McClean P L, Gault V A, Irwin N, et al. Daily administration of the GIP‐R antagonist (Pro3) GIP in streptozotocin‐induced diabetes suggests that insulin‐dependent mechanisms are critical to anti–obesity‐diabetes actions of (Pro3) GIP[J]. Diabetes, Obesity and Metabolism, 2008, 10(4): 336-342.
[8] Irwin N, Hunter K, Flatt P R. Comparison of independent and combined chronic metabolic effects of GIP and CB1 receptor blockade in high-fat fed mice[J]. Peptides, 2008, 29(6): 1036-1041.
[Pro3]-GIP (Mouse)是一种高效的酶抵抗型gastric inhibitory polypeptide (GIP)受体拮抗剂，IC50值为2.6μM[1]。[Pro3]-GIP能够抑制天然 GIP 增加 cAMP 水平以及刺激胰岛素分泌的能力[2]。[Pro3]-GIP已广泛应用于糖尿病和肥胖小鼠模型中，用于改善肥胖表型及β细胞功能[3]。
在体外，1μM的[Pro3]-GIP处理10分钟即可显著抑制GIP受体转染CHL细胞中cAMP的生成[4]。使用1μM的[Pro3]-GIP处理BRIN-BD11细胞20分钟，能显著抑制0.1μM天然GIP诱导的胰岛素释放[5]。
在体内，每日腹腔注射25nmol/kg/day剂量的[Pro3]-GIP连续60天，可显著改善ob/ob小鼠的非空腹血糖水平和胰岛素敏感性[6]。连续20日腹腔注射25nmol/kg/day剂量的[Pro3]-GIP，会加重链脲佐菌素诱导的糖尿病小鼠的高血糖和糖化血红蛋白水平，并降低葡萄糖耐受性和胰岛素敏感性[7]。[Pro3]-GIP（25nmol/kg/day）与AM251（6mg/kg/day）联合用药，通过腹腔注射的方式连续给药22天，降低了高脂饮食小鼠的血糖水平和葡萄糖耐量，并降低了小鼠体重[8]。
| Cell experiment [1]: | |
Cell lines | CHL cells |
Preparation Method | The CHL cells that have been stably transfected with the human GIP receptor were cultured in DMEM medium containing 10% (v/v) fetal bovine serum and 1% (v/v) antibiotics (100U/ml penicillin, 0.1mg/ml streptomycin), and were maintained at 37°C in a culture environment with 5% CO2 and 95% air. The cells were cultured for a further 48h before being loaded at 37°C for 6h with 2µCi of tritiated adenine. Then, the cells were washed twice with HBS buffer (130mM NaCl, 20mM HEPES, 0.9mM NaHPO4, 0.8mM MgSO4, 5.4mM KCl, 1.8mM CaCl2, 25mM glucose and 25µM phenol red; pH 7.4). Subsequently, the cells were exposed to different concentrations (0.001, 0.01, 0.1, 1, 10, 100, and 1000nM) of [Pro3]-GIP at 37°C for 10 minutes. After that, the culture medium was removed and the cells were lysed with 1ml of 5% (v/v) trichloroacetic acid (containing 0.1mM unlabeled cAMP and 0.1mM unlabeled ATP). Finally, the intracellular cAMP was analyzed. |
Reaction Conditions | 0.001, 0.01, 0.1, 1, 10, 100, and 1000nM; 10min |
Applications | [Pro3]-GIP treatment significantly inhibited cAMP generation in CHL cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Obese diabetic (ob/ob) mice |
Preparation Method | The ob/ob mice were housed in an air-conditioned room at 22±2°C, with a 12-hour light:12-hour dark cycle (08:00-20:00). Ob/ob mice were intraperitoneally injected with a 0.9% [w/v] NaCl saline vehicle or [Pro3]-GIP (25nmol/kg/day) once daily at 17:00 for 60 days. Food intake and body weight were recorded daily, and blood glucose and insulin concentrations were monitored every 3-7 days. |
Dosage form | 25nmol/kg/day for 60 days; i.p. |
Applications | [Pro3]-GIP treatment significantly improved non-fasting glucose and insulin sensitivity in ob/ob mice. |
References: | |
| Cas No. | SDF | ||
| 分子式 | C225H342N62O64S | 分子量 | 4971.62 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 201.1 μL | 1.0057 mL | 2.0114 mL |
| 5 mM | 40.2 μL | 201.1 μL | 402.3 μL |
| 10 mM | 20.1 μL | 100.6 μL | 201.1 μL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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