Abstract
The present study was designed to evaluate the protective effect of sulphurenic acid (SA), a pure compound from Antrodia camphorata, on diabetes and hyperlipidemia in an animal model study and to clarify the underlying molecular mechanism. Diabetes was induced by daily 55 mg/kg intraperitoneal injections of streptozotocin (STZ) solution over five days. Diabetic mice were randomly divided into six groups and orally gavaged with SA (at three dosages) or glibenclamide (Glib), fenofibrate (Feno) or vehicle for 3 weeks. Our findings showed that STZ-induced diabetic mice had significantly increased fasting blood glucose, glycated hemoglobin (HbA1C), plasma triglyceride (TG), and total cholesterol (TC) levels (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) but decreased blood insulin, adiponectin, and leptin levels compared to those of the control group (p < 0.001, p < 0.001, and p < 0.001, respectively). Administration of SA to STZ-induced diabetic mice may lower blood glucose but it increased the insulin levels with restoration of the size of the islets of Langerhans cells, implying that SA protected against STZ-induced diabetic states within the pancreas. At the molecular level, SA treatment exerts an increase in skeletal muscle expression levels of membrane glucose transporter 4 (GLUT4) and phospho-Akt to increase the membrane glucose uptake, but the mRNA levels of PEPCK and G6Pase are decreased to inhibit hepatic glucose production, thus leading to its hypoglycemic effect. Moreover, SA may cause hypolipidemic effects not only by enhancing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) with increased fatty acid oxidation but also by reducing lipogenic fatty acid synthase (FAS) as well as reducing mRNA levels of sterol regulatory element binding protein (SREBP)1C and SREBP2 to lower blood TG and TC levels. Our findings demonstrated that SA displayed a protective effect against type 1 diabetes and a hyperlipidemic state in STZ-induced diabetic mice.
Highlights
Type 1 diabetes (T1D), known as juvenile diabetes or insulin-dependent diabetes, is a form of diabetes in which very little or no insulin is produced by the pancreas
There are two major cellular mechanisms to account for the promoted translocation of glucose transporter 4 (GLUT4) to the plasma membrane: insulin signaling through the phosphatidylinositol 3′ kinase (PI3kinase)/Akt pathway and the AMP-activated protein kinase (AMPK) pathway [23,24,25]
Based on one of the possible mechanisms, we investigated whether sulphurenic acid (SA) regulated the expression of genes involved in antidiabetes, lipogenesis, and fatty acid oxidation, including Phosphoenolpyruvate carboxykinase (PEPCK), G6Pase, peroxisome proliferator-activated receptor α (PPARα), and lipogenic fatty acid synthase (FAS) in STZ-induced diabetic mice
Summary
Type 1 diabetes (T1D), known as juvenile diabetes or insulin-dependent diabetes, is a form of diabetes in which very little or no insulin is produced by the pancreas. Insulin stimulates glucose uptake in these cells primarily by inducing the net translocation of GLUT4 from the intracellular storage sites to the plasma membrane. There are two major cellular mechanisms to account for the promoted translocation of GLUT4 to the plasma membrane: insulin signaling through the phosphatidylinositol 3′ kinase (PI3kinase)/Akt pathway and the AMP-activated protein kinase (AMPK) pathway [23,24,25]. Based on one of the possible mechanisms, we investigated whether SA regulated the expression of genes involved in antidiabetes, lipogenesis, and fatty acid oxidation, including PEPCK, G6Pase, peroxisome proliferator-activated receptor α (PPARα), and lipogenic fatty acid synthase (FAS) in STZ-induced diabetic mice
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