Treatment of type 2 diabetes mellitus via reversing insulin resistance and regulating lipid homeostasis in vitro and in vivo using cajanonic acid A

摘要

The present study investigated the effects of cajanonic acid A (CAA), extracted from the leaves of Cajanus cajan (L.) Millsp with a purity of 98.22%, on the regulatory mechanisms of glucose and lipid metabolism. HepG2 cells transfected with a protein-tyrosine phosphatase 1B (PTP1B) overexpression plasmid were established. The cells, induced with insulin resistance by dexamethasone (Dex) treatment, together with type 2 diabetes mellitus (T2DM) model rats and ob/ob mice, were used in the present study. The effects of CAA treatment on the differentiation of 3T3-L1 adipocytes were determined using Oil Red O. The expression levels of insulin signaling factors were detected via reverse transcription-quantitative polymerase chain reaction and western blot analyses. The results revealed that the overexpression of PTP1B contributed to insulin resistance, which was reversed by CAA treatment via inhibiting the activity of PTP1B and by regulating the expression of associated insulin signaling factors. The treatment of cell lines with Dex led to increased expression of PTP1B but decreased glucose consumption, and decreased tyrosine phosphorylation of insulin receptor, insulin receptor substrate 1, and phosphoinositide 3-kinase. Treatment with CAA not only reduced the fasting blood glucose levels and protected organs from damage, but also reduced the serum fasting levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the T2DM rats. CAA treatment also inhibited adipocyte differentiation and decreased the mRNA levels of various adipogenic genes. Furthermore, CAA treatment restored the transduction of insulin signaling by regulating the expression of PTP1B and associated insulin signaling factors. Treatment with CAA also reduced the problems associated with hyperglycemia and hyperlipidemia. In conclusion, CAA may be used to cure T2DM via restoring insulin resistance and preventing obesity.