QiDiTangShen Granules Reduced Diabetic Kidney Injury by Regulating the Phosphorylation Balance of the Tyrosine and Serine Residues of Insulin Receptor Substrate 1

BACKGROUND: Diabetic nephropathy (DN) is a microvascular complication induced by diabetes mellitus (DM), which can affect life quality and long-term prognosis of patients with DM. Angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) are currently recommended for treating DN proteinuria, but patients receiving ACEI/ARB are at risk of elevated serum creatinine or potassium levels. Based on the “yin-yang” theory of traditional Chinese medicine, the present study explored the effect of QiDiTangShen (QDTS) granules on DN and the phosphorylation balance of tyrosine and serine residues of IRS-1. METHODS: In this experiment, db/db mice were used as an animal model for type 2 diabetic nephropathy. The intervention (QDTS granules and valsartan) started when the mice were 12 weeks old. C57BL/6 mice were used as normal control. The urine albumin excretion ratio (UAER) was measured by enzyme-linked immunosorbent assay (ELISA) before and after the intervention. The IRS-1, PI3K, Akt, and MAPK proteins expression and the phosphorylation levels were detected by western blot. RESULTS: QDTS granules reduced the 24-h urinary albumin excretion rate (UAE) in db/db mice with type 2 DM and attenuated the pathological changes of the kidney. QDTS granules also increased the activation level of the PI3K/Akt signaling pathway and reduced insulin resistance. In addition, QDTS granules inhibited the activation of ERK and p38MAPK and decreased the phosphorylation ratio of Ser307/Tyr896 of IRS-1 in renal tissue. CONCLUSIONS: QDTS granules reduced DM-induced renal injury by improving insulin sensitivity via suppressing MAPK signaling and restoring the phosphorylation balance of tyrosine/serine of IRS-1.