Zhenqing recipe relieves diabetic nephropathy through the SIK1/SREBP-1c axis in type 2 diabetic rats

Salt-inducible kinase 1 (SIK1) plays an important role in lipid metabolism, which inhibits lipid synthesis by directly phosphorylating multiple serine residue sites of sterol regulatory element-binding protein 1c (SREBP-1c). This study examined potential therapeutic effect of a Chinese herbal medicine Zhenqing Recipe (ZQR) and metformin on diabetic nephropathy and investigated whether the SIK1/SREBP-1c axis is involved.

The rat model of type 2 diabetes was developed by high-sucrose plus high fat diet for one month combined with low-dose Streptozocin intraperitoneal injection for three days, after which the presence of hyperglycemia and hyperlipidemia was examined to validate the model. The diabetic rats were then randomly allocated to diabetic groups treated by either ZQR or metformin, and normal rats receiving normal diet were included as a control group. Metabolic parameters, renal function, and renal triglyceride were examined and compared between groups.

After a treatment of 12 weeks, ZQR and metformin significantly reduced serum glucose and triglyceride, inhibited diabetic nephropathy and improved renal function. The mRNA level of SIK1 was significantly lower in the diabetic rats than that in the control group, while the expression of SREBP-1c had an opposite pattern. However, after receiving ZQR or metformin treatment, the SIK1 level in diabetic rats increased and the SREBP-1c level was downregulated. Consistent results were observed at the protein level.

The data suggested that similar to metformin, ZQR could alleviate diabetic nephropathy through SIK1/SREBP-1c axis.