Department of Geraeology, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Peptides. 2011 Feb;32(2):209-15. doi: 10.1016/j.peptides.2010.11.011. Epub 2010 Nov 19.
Ghrelin has wide effects on cardiovascular and endocrine system. The aims of this study are to investigate the direct damage effect of high glucose and high palmitate on cardiomyocyte, and to study the effect of ghrelin on insulin resistance induced by glucotoxicity/lipotoxicity in cardiomyocyte and the possible mechanism underlying the cardioprotective activities of ghrelin. The changes of [(3)H]-2-deoxy-d-glucose ((3)H-G) intake rates were detected by isotope tracer method and the gene expressions in insulin signal transduction pathway were detected by real-time PCR and Western blot assay. The (3)H-G intake rate significantly reduced in high glucose (25mmol/l) or high palmitate (0.5mmol/l) treated primary rat ventricular myocytes. After the treatment of ghrelin (10(-7)mol/l), the (3)H-G intake rate recovered to the normal level. In addition, the phosphorylation of AKT occurred in 10min and was the highest in 30min after the stimulation with ghrelin, which can be blocked by phosphoinositide 3-kinase (PI3K) inhibitor, LY2940002. Ghrelin also increased the mRNA levels of glucose transporter 4 (GLUT4), peroxisome proliferators (PPARr) and AMP activated protein kinase (AMPK) genes in insulin signal transduction pathway. These results indicate that the direct damage of high glucose and high palmitate on cardiomyocyte might be through insulin resistance (IR). Ghrelin can inhibit gluco/lipotoxicity induced insulin resistance by PI3K/AKT pathway. This may provide a clue for therapy for myocardial disease in diabetes mellitus.
生长激素释放肽对心血管和内分泌系统有广泛的影响。本研究旨在探讨高糖和高棕榈酸对心肌细胞的直接损伤作用，以及生长激素释放肽对糖毒性/脂毒性诱导的心肌细胞胰岛素抵抗的影响及其可能的机制。采用同位素示踪法检测[（3）H]-2-脱氧-d-葡萄糖（（3）H-G）摄取率，实时 PCR 和 Western blot 检测胰岛素信号转导通路中的基因表达。高葡萄糖（25mmol/L）或高棕榈酸（0.5mmol/L）处理原代大鼠心室肌细胞后，（3）H-G 摄取率明显降低。用生长激素释放肽（10（-7）mol/L）处理后，（3）H-G 摄取率恢复正常水平。此外，生长激素刺激 10min 后 AKT 磷酸化发生，30min 时达到高峰，可被磷脂酰肌醇 3-激酶（PI3K）抑制剂 LY2940002 阻断。生长激素释放肽还增加了胰岛素信号转导通路中葡萄糖转运蛋白 4（GLUT4）、过氧化物酶体增殖物激活受体 r（PPARr）和 AMP 激活蛋白激酶（AMPK）基因的 mRNA 水平。这些结果表明，高糖和高棕榈酸对心肌细胞的直接损伤可能是通过胰岛素抵抗（IR）。生长激素释放肽通过 PI3K/AKT 通路抑制糖脂毒性诱导的胰岛素抵抗。这可能为糖尿病心肌疾病的治疗提供线索。
