Searching for phytoinsulins as cardiovascular protector in metabolic syndrome.

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.