| 名稱 | Metformin hydrochloride |
| 描述 | Metformin hydrochloride (1,1-Dimethylbiguanide hydrochloride) is an AMPK activator with blood-brain barrier permeability. Metformin hydrochloride may improve glycemic control by increasing insulin sensitivity and decreasing intestinal glucose uptake, and is commonly used in type 2 diabetes research. |
| 細胞實驗 | Hepatocytes were isolated from male Sprague Dawley (SD) rats by collagenase digestion. For the AMPK assay, cells were seeded in six-well plates at 1.5 × 10^6 cells/well in DMEM containing 100 U/ml penicillin, 100 μg/ml streptomycin, 10% FBS, 100 nM insulin, 100 nM dexamethasone, and 5 μg/ml transferrin for 4 hours. Cells were then cultured in serum-free DMEM for 16 hours followed by treatment for 1 hour or 7 hours with control medium, 5-aminoimidazole carboxamide riboside (AICAR), or metformin at concentrations indicated. For a 39-hour treatment, cells for both control and metformin (10 or 20 μM) groups were cultured in DMEM plus 5% FBS and 100 nM insulin, and the fresh control and metformin-containing medium were replaced every 12 hours (last medium change was 3 hours before harvest). After treatment, the cells were directly lysed in digitonin-containing and phosphatase inhibitor–containing buffer A, followed by precipitation with ammonium sulfate at 35% saturation. AMPK activity was determined by measurement of phosphorylation of a synthetic peptide substrate, SAMS (HMRSAMSGLHLVKRR). For ACC assay, the 35% ammonium sulfate precipitate from digitonin-lysed hepatocytes (4 μg each) was used for determination of ACC activity via 14CO2 fixation in the presence of 20 mM citrate as done previously. For fatty acid oxidation, the oxidation of 14C-oleate to acid-soluble products was performed as done previously, but in medium M199 in the absence of albumin [1]. |
| 動物實驗 | Oral gavage was used to administer 1 ml of metformin (100 mg/ml) or water alone to male SD rats (300–350 g, n = 7–8). Rats were treated once or twice a day for 5 days. Rats were starved for 20 hours and then re-fed for 2 hours before the final dose; 4 hours after the final dose, the animals were anesthetized and livers rapidly removed by freeze clamping followed by blood withdrawal. RNA was prepared from the freeze-clamped liver by RNA isolation reagent. Nuclear extracts were prepared from a pool of seven rat livers. Glucose levels were determined using the standard glucose oxidase assay kit; β-hydroxybutyrate concentrations were assayed by measuring the reduction of NAD to NADH with a standard assay kit. FFA levels were measured with the assay kit [1]. MCF10A-ER-Src cells (5 × 10^6) were injected into the right flank of 18 female nu/nu mice, all of which developed tumors in 10 d with a size of ～100 mm^3. The mice were randomly distributed into six groups (three mice/group) that were untreated or treated by intratumoral injections every 5 d (four cycles) with 1 mg/kg or 4 mg/kg doxorubicin, 200 μg/mL metformin (diluted in the drinking water), or the combination. In another experiment, LNCaP and DU145 prostate cancer cells (5 × 10^6) were injected into the right flank of 12 female nu/nu mice, all of which developed tumors in 10 d with a size of ～75 mm^3. The mice were randomly distributed into four groups that were untreated or treated by intratumoral injections every 5 d (four cycles) with 4 mg/kg doxorubicin and/or 200 μg/mL metformin. In another experiment, A375 and MDA-MB-435 melanoma cells (7 × 10^6) were injected into the right flank of 12 female nu/nu mice, all of which developed tumors in 10 d with a size of ～50 mm3. The mice were randomly distributed into four groups that were untreated or treated by intratumoral injections every 5 d (four cycles) with 10 mg/kg cisplatin and/or 200 μg/mL metformin.Finally, SNU-449 liver cancer cells (10^7) were injected into the right flank of 12 female nu/nu mice, all of which developed tumors in 10 d with a size of ～50 mm^3. The mice were randomly distributed into four groups that were untreated or treated by intratumoral injections every 5 d (four cycles) with 10 mg/kg cisplatin and/or 200 μg/mL metformin. Tumor volume (mean ± SD) was measured at various times after the initial injection [3]. |
| 體外活性 | 方法: 卵巢癌細胞 A2780 和 SKOV3 用 Metformin hydrochloride (0.001-50 mM) 處理 24-48 h，使用 MTS 方法檢測細胞活力。
結果: 微摩爾濃度的 Metformin 在統(tǒng)計學上不會降低 A2780 或 SKOV3 細胞系的生存能力。在 48 h 時，毫摩爾濃度會導致細胞死亡。[1]
方法: 人結直腸癌細胞 HCT29 用 Metformin hydrochloride (0.6 mM) 處理 90 h，使用 wound healing assay 和 chamber invasion assay 檢測細胞運動情況。
結果: Metformin 抑制 HCT29 細胞的遷移和侵襲。Metformin 降低腫瘤細胞的運動能力。[2] |
| 體內活性 | 方法: 為建立 Metformin 誘導腹瀉的模型，將 Metformin hydrochloride (125-500 mg/kg) 口服給藥給健康和糖尿病肥胖 db/db 的 C57BL/6J 小鼠，每天兩次，持續(xù)十三天。
結果: 1000?mg/kg/天的 Metformin 顯著增加了糞便水分含量。盡管在健康 C57BL/6J 小鼠中未觀察到腹瀉癥狀，但相同劑量的 Metformin 在糖尿病肥胖 db/db 小鼠中誘導嚴重腹瀉。[3]
方法: 為研究在輻射損傷中的保護作用，將 Metformin hydrochloride (200 mg/kg，每天一次持續(xù)三天) 口服給藥給 BALB/c 小鼠，隨后暴露于 6-8 Gy 的 γ 射線。
結果: 在暴露于輻射前給藥時，Metformin 可以延長暴露于 8 Gy-TBI 的小鼠的生存期，并提高暴露于 6 Gy-TBI 小鼠的生存率。Metformin 預處理可以減輕輻射損傷。[4] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : 193.21 mM
DMSO : 15 mg/mL (90.56 mM), Sonication is recommended.
|
| 關鍵字 | insulin | Autophagy | 1,1-Dimethylbiguanide | Inhibitor | 1, 1-Dimethylbiguanide Hydrochloride | respiratory | AMP-activated protein kinase | blood-brain | inhibit | chain | Mitochondrial Autophagy | sensitivity | AMPK | liver | Metformin hydrochloride | Metformin | Metformin Hydrochloride | barrier | type | Mitophagy | 1,1-Dimethylbiguanide Hydrochloride | diabetes | mitochondrial |
| 相關產品 | Chitosan oligosaccharide | Guanidine hydrochloride | Hydroxychloroquine |
| 相關庫 | 神經(jīng)保護化合物庫 | 經(jīng)典已知活性庫 | 抗癌上市藥物庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | FDA 上市藥物庫 | FDA 上市激酶抑制劑庫 |