Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi'an 710032, China.
Curr Pharm Des. 2013;19(27):4848-58. doi: 10.2174/1381612811319270007.
Metabolic syndrome is well known to increase the risk of cardiovascular disease and diabetes. As the key feature of metabolic syndrome, insulin resistance occurs when target tissues cannot respond properly to insulin and develops in multiple organs, including the vasculature and heart. Accumulating evidence has suggested insulin-induced PI3K-Akt-eNOS survival signaling as a potent therapeutic target for cardiovascular disorders and highlighted the impaired survival signaling as a key link between insulin resistance and cardiovascular disease. However, long-term insulin treatment is inconvenient and may increase the risk of hypoglycemia. More importantly, the effects of insulin are significantly blunted in patients with insulin resistance due to the pathway-specific impairment of PI3K-Akt signaling, and exogenous chronic insulin administration may lead to the over-activation of Ras-MAPK signaling which may result in unwanted side effects. Our recent study has shown that some Chinese medicinal herbs can directly activate PI3K-Akt-eNOS survival signals and improve tissue insulin sensitivity to exert endothelial and cardiac protective effects in diabetic animals. These herbs or phytoinsulins as we named, targeting insulin-activated cell survival signals and exert insulin-like actions, have promising beneficial effects on prevention and treatment of diabetes- and insulin resistance-induced cardiovascular disorders. Another advantage of phytoinsulins is that they generally exert multiple actions, including mild blood glucose-lowering effect, pancreatic β cells protection and adipogenesis reduction, for better cardiovascular protection. In this review, we discussed our strategies of searching for phytoinsulins and their potential beneficial effects in the treatment of metabolic syndrome, especially their values in prevention of diabetic cardiovascular disease.
代谢综合征众所周知会增加心血管疾病和糖尿病的风险。作为代谢综合征的关键特征，胰岛素抵抗发生在靶组织对胰岛素不能正常反应，并在多个器官中发展，包括血管和心脏。越来越多的证据表明，胰岛素诱导的 PI3K-Akt-eNOS 生存信号是心血管疾病治疗的有效靶点，并强调了生存信号受损是胰岛素抵抗与心血管疾病之间的关键联系。然而，长期胰岛素治疗不方便，并且可能增加低血糖的风险。更重要的是，由于 PI3K-Akt 信号通路的特异性损伤，胰岛素抵抗患者的胰岛素作用明显减弱，外源性慢性胰岛素给药可能导致 Ras-MAPK 信号过度激活，从而导致不必要的副作用。我们最近的研究表明，一些中药可以直接激活 PI3K-Akt-eNOS 生存信号，提高组织胰岛素敏感性，从而在糖尿病动物中发挥内皮和心脏保护作用。这些草药或我们命名的植物胰岛素，针对胰岛素激活的细胞生存信号并发挥胰岛素样作用，在预防和治疗糖尿病和胰岛素抵抗引起的心血管疾病方面具有有希望的有益效果。植物胰岛素的另一个优点是它们通常发挥多种作用，包括轻度降低血糖、保护胰岛β细胞和减少脂肪生成，从而更好地保护心血管。在这篇综述中，我们讨论了我们寻找植物胰岛素的策略及其在治疗代谢综合征方面的潜在有益作用，特别是它们在预防糖尿病性心血管疾病方面的价值。
