Ligustilide alleviates the insulin resistance, lipid accumulation, and pathological injury with elevated phosphorylated AMPK level in rats with diabetes mellitus

Abstract

Background Diabetes mellitus (DM) is one of the major risk factors of disability and death worldwide. Despite of the protective role of ligustilide (LIG) in many cell types, we aimed to investigate whether LIG could be a potential to treat DM. Methods Sprague Dawley rats were randomly assigned to five groups. Rats except control were raised on a high-fat diet (HFD). Streptozotocin was intraperitoneally injected into HFD-fed rats to construct DM model. Rats in the LIG intervention groups received intraperitoneal injection of LIG (10, 20, and 40 mg/kg) post-induction of DM. Blood glucose, plasma insulin (p-insulin), adiponectin, HbA1C%, obesity index, HOMA-IR, and biochemical parameters were estimated. Histopathological analysis and apoptosis in liver and kidney, along with proliferation and apoptosis of islet β-cells, were analyzed. Expression of CPT-1 and ACC, and phosphorylation of Nrf2 and AMPKα1, were finally assessed. Results DM-induced alterations were all relived by LIG intervention. In brief, obesity index, glucose level, P-insulin content, HbA1C, and HOMA-IR were lowered while adiponectin level was elevated. Meanwhile, levels of TC, TG, ALT, and AST were decreased in the LIG intervention groups, along with up-regulated CPT-1 level and down-regulated ACC level. Pathological changes in liver and kidney tissues were alleviated, and apoptotic cells were reduced by LIG treatment. For islet β-cells, LIG up-regulated Ki67 and c-Myc expression, and mitigated ratios of Bax/Bcl-2 and cleaved cas3(9)/cas3(9). Finally, LIG could promote phosphorylation of Nrf2 and AMPKα1. Conclusions LIG alleviated the insulin resistance, lipid accumulation, and pathological injury with the activation of AMPK pathway in DM rats.