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Gancao Xiexin Decoction exerts anti-hyperglycemic and anti-hyperlipidemic effects in type 2 diabetes mellitus rats via IRS2/PI3K/Akt pathway
Abstract
Purpose: To evaluate the anti-diabetic effect of the classical traditional Chinese medicine (TCM) formulation, Gancao Xiexin Decoction (GCXXT), as well as unravel its mechanism of action.
Methods: A rat model with type 2 diabetes mellitus (T2DM) was induced through ingestion of a high-fat diet, followed by injection of streptozocin. The rats were divided into six groups: control, model, metformin, GCXXT-L (4 g/kg), GCXXT-M (8 g/kg) and GCXXT-H (12 g/kg) groups, each with six rats. The metabolic parameters related to T2DM, expression and phosphorylation levels of IRS2, PI3K, and Akt protein were determined by western blot.
Results: GCXXT, especially at the high dose (12 g/kg), not only significantly reduced the levels of fasting blood glucose, hemoglobin A1c, and advanced glycation end products, but also increased the fasting insulin level, HOMA-β index, β-cell mass, and oral glucose tolerance levels in T2DM rats (p < 0.05). Furthermore, GCXXT exhibited anti-hyperlipidemic effect by elevating high-density lipoprotein cholesterol level and lowering total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels (p < 0.05). Phosphorylated IRS2, PI3K, Akt protein in the pancreas, liver, and adipose tissues of T2DM rats were significantly increased by GCXXT (p < 0.05), whereas total IRS2, PI3K, and Akt protein levels did not change significantly.
Conclusion: GCXXT exerts anti-hyperglycemic and anti-hyperlipidemic effects, in part, by regulating the IRS2/PI3K/Akt signaling pathway in the pancreas, liver, and adipose tissues of T2DM rats. Thus, GCXXT is a potential agent for the management of T2DM but clinical studies are required to ascertain this
