Abstract
Type 2 diabetes (T2D) with high morbidity and mortality is characterized by abnormal glucose and lipid metabolism due in part to insulin resistance in liver, which lead to elevated hyperglycemia and hyperlipidemia. This study sough to explore the effects of corosolic acid (CA) in different T2D models and explored the underlying mechanism. Separated from Eriobotrya japonica leaves, CA purity was above 95% measured by a HPLC method. Compared with cAMP and DEX induced T2D HepG2 model, CA significantly stimulated glucose consumption and improved glycogen accumulation by inhibiting PEPCK mRNA expression. And in cAMP and DEX induced T2D zebrafish model, CA reduced glycogen degradation and increased glucose consumption by regulating some key enzymes in carbon metabolism including GLUT1, GLUT2, GLUT3, LDHA, LDHB, GP, G6Pase, GYS1, and PFKFB3. In addition, insulin receptor signals were also involved in CA-regulated hypoglycemic action. Furthermore, in STZ-induced T2D rat model, compared with diabetic control groups, CA remarkably downregulated the levels of serum lipid, blood glucose, ICAM-1, malonaldehyde and insulin resistance index, while upregulated SOD activity and impaired glucose tolerance. In a conclusion, CA can regulate glucose and lipid metabolic adaptation in T2D like HepG2, zebrafish and rat models partly through reducing inflammation and oxidative stress and suppressing PEPCK.
Highlights
Type 2 diabetes(T2D) is a widely heterogeneous disorder featured by fasting and post-prandial hyperglycemia and progression of insulin resistance, which has affected increasing number of populations and become one of the most costly and burdensome diseases[1]
The bioactive products derived from plants, which are with the benefits of availability of materials, affordability, relatively cheap and little or no side effects[39], are being considered to be a promising source to design effective therapeutic agents for fatal disease including cancer, cardiovascular and diabetes mellitus[40]
Our results revealed that corosolic acid (CA) alleviated the weight loss of diabetic rats, significantly reduced biochemical parameters including fasting blood glucose (FBG), glycated serum protein (GSP), total cholesterol (TC), TG, low density lipoprotein-cholesterol (LDL-C) and FFA level of T2D rats, and improved high density lipoprotein-cholesterol (HDL-C) level
Summary
Type 2 diabetes(T2D) is a widely heterogeneous disorder featured by fasting and post-prandial hyperglycemia and progression of insulin resistance, which has affected increasing number of populations and become one of the most costly and burdensome diseases[1]. Corosolic acid (2α,3β-2,3-dihydroxy-urs-12-en-28-oic acid) is a natural pentacyclic triterpene discovered in traditional Asian medical herbs such as Lagerstroemia speciose[12,13], Eriobotrta japonica[14], Tiarella polyphylla[15], which has attracted much attention for its antidiabetic and anti-lipid oxidative activity in some animal experiments and clinical trials, including development of glucose metabolism by declining insulin resistance in mice and reducing on post-challenge plasma glucose levels in human[16,17,18,19,20,21,22,23,24,25]. Due to high homology with human, zebrafish has been widely used as a model organism to research on biological process of vertebrate These studies include malignant neoplasms, cardiovascular diseases, immune system diseases, antioxidant stress and diabetes[26]. It’s been reported that zebrafish regulated glucose metabolism by producing insulin, glucagon and other important proteins, such as PEPCK, which identified similar regulation patterns and activity in mammalian models[27,28]
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