中医药通过调节肝糖异生从脾论治糖尿病研究进展

Advances in mechanism research of anti-diabetic traditional Chinese medicine from spleen in inhibiting hepatic gluconeogenesis

肝糖异生异常增多是糖尿病发生重要机制之一,胰岛素抵抗是2型糖尿病的病理基础,肝脏胰岛素抵抗导致肝糖异生增加。磷酸烯醇式丙酮酸羧激酶(PEPCK)和葡萄糖-6-磷酸酶(G6Pase)是肝糖异生关键酶,CREB、TORC2、PGC-1ɑ等转录因子启动PEPCK和G6Pase转录、促进肝糖异生,亦是药物调节血糖作用的分子靶点。从中医角度来讲,过度肝糖异生与脾失健运和脾不藏精有关。"从脾论治",通过调节脾的运化功能及"藏精"功能治疗消渴气阴两虚证、脾虚湿盛证、湿热互结证,以减少肝糖异生成为近年中医药治疗糖尿病研究热点。多种中药复方通过益气健脾、养阴生津、健脾祛湿、清热利湿等,改善消渴"三多一少"症状、降低血糖,其活性成分经现代医学研究证实可改善胰岛素抵抗、抑制肝糖异生分子通路,为研究中医药通过肝糖异生防治糖尿病提供了更多实证依据。

Abnormally increased hepatic gluconeogenesis plays an important role in diabetes. Insulin resistance is the pathological basis of T2 DM, leading to an increase in hepatic gluconeogenesis. PEPCK and G6 Pase, two key enzymes of hepatic gluconeogenesis, are activated by transcription factors such as CREB, TORC2 and PGC-1ɑ, which are also molecular targets of medicines in regulating blood glucose. From the perspective of traditional Chinese medicine, excessive hepatic gluconeogenesis is associated with dysfunction of the spleen in transport and storing essence. In recent years, "treatment from spleen", by the regulation of spleen transport and storing essence function to treat diabetes of deficiency of Qi and Yin syndrome, spleen deficiency and dampness syndrome and damp-heat syndrome to reduce the hepatic gluconeogenesis, has become a hot spot of diabetes research. The anti-diabetic activity of traditional Chinese medicines has been proved and their mechanisms in improving insulin resistance and inhibiting transcription of hepatic gluconeogenesis have been identified, through treating diabetes from spleen, replenishing vital energy, dispelling dampness and clearing heat and removing dampness. These researches holds extensive promise for the clinical application of traditional Chinese medicine.