Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, and most patients with T2DM develop nonalcoholic fatty liver disease (NAFLD). Both diseases are closely linked to insulin resistance (IR). Our previous studies demonstrated that Ruellia tuberosa L. (RTL) extract significantly enhanced glucose uptake in the skeletal muscles and ameliorated hyperglycemia and IR in T2DM rats. We proposed that RTL might be via enhancing hepatic antioxidant capacity. However, the potent RTL bioactivity remains unidentified. In this study, we investigated the effects of RTL on glucose uptake, IR, and lipid accumulation in vitro to mimic the T2DM accompanied by the NAFLD paradigm. FL83B mouse hepatocytes were treated with tumor necrosis factor-α (TNF-α) to induce IR, coincubated with oleic acid (OA) to induce lipid accumulation, and then, treated with RTL fractions, fractionated with n-hexane or ethyl acetate (EA), from column chromatography, and analyzed by thin-layer chromatography. Our results showed that the ethyl acetate fraction (EAf2) from RTL significantly increased glucose uptake and suppressed lipid accumulation in TNF-α plus OA-treated FL83B cells. Western blot analysis showed that EAf2 from RTL ameliorated IR by upregulating the expression of insulin-signaling-related proteins, including protein kinase B, glucose transporter-2, and peroxisome proliferator-activated receptor alpha in TNF-α plus OA-treated FL83B cells. The results of this study suggest that EAf2 from RTL may improve hepatic glucose uptake and alleviate lipid accumulation by ameliorating and suppressing the hepatic insulin signaling and lipogenesis pathways, respectively, in hepatocytes.
Highlights
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, insufficient insulin secretion or action, or insulin resistance (IR). ese conditions cause abnormalities in lipid, carbohydrate, protein, water, and electrolyte functions
In the present study, we aimed to utilize the tumor necrosis factor-α (TNF-α)-induced IR combined with the oleic acid (OA)-induced steatosis paradigm to identify the active ingredients of Ruellia tuberosa L. (RTL) extracts through thin-layer chromatography (TLC), to improve glucose intake and inhibit lipogenesis, and to clarify the underlying mechanisms of metabolism in FL83B cells
An evaluation of the 2-NBDG uptake was performed to assess the improvement of glucose uptake in FL83B cells. e EAf4 fraction improved glucose uptake of FL83B mouse hepatocytes compared with the control group (p 0.030) or compared with the TNFα-induced IR group (p 0.013)
Summary
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, insufficient insulin secretion or action, or insulin resistance (IR). ese conditions cause abnormalities in lipid, carbohydrate, protein, water, and electrolyte functions. Long-term hyperglycemic conditions increase both oxidative stress and inflammatory responses, leading to an increased risk of chronic inflammatory systemic diseases and their respective complications [1,2,3]. Approximately 70% of patients with T2DM present with nonalcoholic fatty liver disease (NAFLD), which is a bidirectional relationship [4, 5]. If IR occurs, the lipolysis rate of visceral fat cells increases, which leads to an increased content of free fatty acids (FFAs) in the blood. When glycerol and fatty acids enter the liver, this results in increased lipogenesis and excess lipid accumulation in liver cells, eventually causing fatty liver disease. Current T2DM- or NAFLD-related studies follow combined approaches, and these researchers’ paradigm is more in line with the actual condition of such patients
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