Regulation of TCF7L2 in cardiac myocytes by diabetic conditions  

出　　处：《中国药理学通报》2015年第B11期170-171,共2页Chinese Pharmacological Bulletin

摘　　要：Backgrounds： TCF7L2 is a member of T cell factor （TCF）/lymphoid enhancer factor （LEF） family transcription- al factors that interact with β-catenin in canonical Wnt signaling. TCF7L2 plays important roles in metabolism and glucose homeostasis. Genetic variations of TCFTL2 are associated with increased risks of Diabetes Mellitus. It is not known if diabetic conditions also modulate TCFTL2 expression in the heart. Methods TCFTL2 and β-catenin ex- pression was investigated by Western blot, RT-PCR and immunofluorescence in HL-1 cells and neonatal rat ventric-ular myocytes （NRVM） treated with 14 mmol · L 1 mannitol （ M）, 25 mmol· L^-1 glucose （ G）, 10 nmol · L insulin （I）, and G plus I （G ＋ I）. In addition, TCF7L2 and β-catenin levels were examined by Western blot in the heart of B6. Cg-m Leprdb/ ＋ ＋/J （db） and C57B1/6J （C57） mice 4 hours after intraperitoneal injections of 1.5 IU · kg^-1 insulin. Blood glucose levels were determined on blood drawn from the tail vein. Result The ex- pression of TCF7L2 and β-catenin was higher in nucleus of db mice hearts than C57 hearts. Insulin treatment de- creased TCF7L2 and β-catenin level in C57 hearts. Paradoxically, TCF7L2 and β-catenin was further increased by insulin in db hearts. In HL-1 cells and NRVMs, TCF7L2 started to decrease at one hour and remained lower up to 24 hours after insulin treatment compared to untreated controls. In contrast, G increased TCF7L2 expression at 1, 6 and 24 hours after treatment relative to M. Insulin could decrease TCF7L2 at 1 and 6 hours, but failed to do so at 24 hours in G ＋ I. At 48 hours, no difference in TCF7L2 expression was observed among different treatment groups. The immunostaining showed β-catenin translocated to the nucleus and colocalized with TCF7L2 in G at 6 hours and 24 hours. Insulin could inhibit the TCF7L2 and β-catenin expression as well as β-catenin translocation at 6 hours but could not do so at 24 hours in G ＋ I. Conclusion Insulin regulation of TCF7L2 is inte

关 键 词：糖尿病心肌病 心肌细胞核 β-catenin 监管条件 Β-连环蛋白 胰岛素治疗 HL-1细胞 糖尿病小鼠 

分 类 号：R587.2[医药卫生—内分泌] R321-5[医药卫生—内科学]