Pathological cardiac remodeling is a leading cause of mortality in diabetic patients. Given the glucose and lipid metabolism disorders (GLD) in diabetic patients, it is urgent to conduct a comprehensive study of the myocardial damage under GLD and find key mechanisms. Apolipoprotein E knockout (ApoE^-/-) mice, low-density lipoprotein receptor heterozygote (Ldlr^+/-) syrian golden hamsters or H9C2 cells were used to construct GLD models -. And GLD significantly promoted cardiomyocyte fibrosis, apoptosis and hypertrophy in vivo and in vitro, while inhibition of galectin-3 (Gal-3) could significantly reverse this process. Then, the signal transmission pathways were determined. It was found that GLD considerably inhibited the phosphorylation of Akt at Thr³⁰⁸ / Ser⁴⁷³, whereas the silencing of Gal-3 could reverse the inhibition of Akt activity through PI3K-Akt^Thr308 and AMPK-mTOR2-Akt^Ser473 pathways. Finally, the PI3K, mTOR, AMPK inhibitor and Akt activator were used to investigate the role of pathways in regulating cardiac remodeling. Phospho-Akt^Thr308 could mediate myocardial fibrosis, while myocardial apoptosis and hypertrophy were regulated by both phospho-Akt^Thr308 and phospho-Akt^Ser473. In conclusion, Gal-3 was an important regulatory factor in GLD-induced cardiac remodeling, and Gal-3 could suppress the phosphorylation of Akt at different sites in mediating cardiomyocyte fibrosis, apoptosis and hypertrophy.

中文翻译：

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Galectin-3 通过抑制 Akt 激活的两条途径介导葡萄糖和脂质代谢受损引起的心脏重塑


病理性心脏重塑是糖尿病患者死亡的主要原因。鉴于糖尿病患者存在糖脂代谢紊乱（GLD），迫切需要对GLD引起的心肌损伤进行全面研究并寻找关键机制。采用载脂蛋白E基因敲除(ApoE ^-/- )小鼠、低密度脂蛋白受体杂合子(Ldlr ^+/- )叙利亚金仓鼠或H9C2细胞构建GLD模型-。 GLD在体内外均显着促进心肌细胞纤维化、凋亡和肥大，而抑制半乳糖凝集素3（Gal-3）可显着逆转这一过程。然后，确定了信号传输途径。研究发现，GLD 显着抑制 Akt Thr ³⁰⁸ / Ser ⁴⁷³的磷酸化，而沉默 Gal-3 可以通过 PI3K-Akt ^Thr308和 AMPK-mTOR2-Akt ^Ser473途径逆转 Akt 活性的抑制。最后，利用PI3K、mTOR、AMPK抑制剂和Akt激活剂研究通路在调节心脏重构中的作用。磷酸化Akt ^Thr308可介导心肌纤维化，而磷酸化Akt ^Thr308和磷酸化Akt ^Ser473均能调节心肌细胞凋亡和肥大。总之，Gal-3是GLD诱导的心脏重构的重要调节因子，Gal-3可以抑制Akt不同位点的磷酸化，介导心肌细胞纤维化、凋亡和肥大。