PF-739 is an AMPK activator. PF-739 reduces plasma glucose levels by activating all 12 heterotrimeric AMPK complexes. PF-739 can be used in research related to type 2 diabetes and metabolic syndrome[1-2].
In vitro, PF-739 (0-10µM) treatment of hepatocytes and skeletal muscle myotubes. PF-739 increased phosphorylation of Acetyl-CoA carboxylase (ACC) and inhibition of de novo lipogenesis in hepatocytes[3]. PF-739 (10µM) treatment of isolated mouse extensor digitorum longus (EDL) and soleus muscle fibers for 30 minutes. PF-739 significantly increased glucose uptake and promoted glycogen accumulation[4].
In vivo, PF-739 (10-300mg/kg; orally, 30-100mg/kg; subcutaneously) treatment of diet-induced obese (DIO) mice and db/db diabetic mice rapidly lowered blood glucose levels within 1-6 hours after administration. PF-739 increased the whole-body glucose disposal rate and enhanced glycogen synthesis, labeling of glycolytic intermediates, and mitochondrial content in skeletal muscle[3]. A single subcutaneous injection of PF-739 (100mg/kg) in diet-induced obese wild-type and inducible skeletal muscle-specific AMPK α1/α2 knockout mice. PF-739 significantly increased the glucose disposal rate and lowered blood glucose in wild-type mice, an effect that was absent in AMPK knockout mice[4].
References:
[1] Weihrauch M, Handschin C. Pharmacological targeting of exercise adaptations in skeletal muscle: Benefits and pitfalls. Biochem Pharmacol. 2018 Jan;147:211-220.
[2] Aledavood E, Gheeraert A, Forte A, et al. Elucidating the Activation Mechanism of AMPK by Direct Pan-Activator PF-739. Front Mol Biosci. 2021 Nov 5;8:760026.
[3] Cokorinos EC, Delmore J, Reyes AR, et al. Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice. Cell Metab. 2017 May 2;25(5):1147-1159.e10.
[4] Esquejo RM, Albuquerque B, Sher A, et al. AMPK activation is sufficient to increase skeletal muscle glucose uptake and glycogen synthesis but is not required for contraction-mediated increases in glucose metabolism. Heliyon. 2022 Oct 14;8(10):e11091.
PF-739是一种AMPK激活剂，通过激活12种异三聚体AMPK复合物来降低血浆葡萄糖水平。PF-739可用于2型糖尿病和代谢综合征的相关研究[1-2]。
在体外，PF-739（0-10µM）处理肝细胞及骨骼肌肌管细胞，导致乙酰辅酶A羧化酶（ACC）磷酸化增加，并抑制肝细胞新生脂肪生成[3]。PF-739（10µM）处理小鼠离体伸趾长肌（EDL）及比目鱼肌纤维30分钟，显著增加其葡萄糖摄取，同时促进糖原积累[4]。
在体内，PF-739（10-300mg/kg；口服，30-100mg/kg；皮下注射）处理饮食诱导肥胖（DIO）小鼠、db/db糖尿病小鼠。PF-739在给药后1-6小时内可快速降低血糖水平，PF-739可增加全身葡萄糖处置率，并在骨骼肌中增加糖原合成、糖酵解中间产物的标记以及线粒体含量[3]。PF-739（100mg/kg）单次皮下注射于饮食诱导肥胖的野生型及可诱导骨骼肌特异性AMPK α1/α2敲除小鼠。PF-739显著增加了野生型小鼠的葡萄糖处理率并降低了血糖，且此效应在AMPK敲除小鼠中消失[4]。