Abstract
In this study, we observed the effect of D-chiro-inositol (DCI) on glucose consumption in type 2 diabetic db/db mice, and investigated the relevant mechanism. We discovered that the stability of 24-h blood glucose under the nonfasting condition and decreased glucose tolerance were both alleviated after treatment with DCI. Moreover, the content of glycosylated protein and advanced glycation end products in the serum was reduced, the damage in the liver tissue was alleviated, and the synthesis of liver glycogen was significantly promoted. In addition, DCI increased the expression of insulin receptor substrate 2 (IRS2), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), glucose transporters 4 (GLUT4), and phospho-AKT (S473) protein. In contrast, DCI decreased the expression level of glycogen synthase kinase 3β (GSK3β) protein in liver tissue to various degrees, as shown by immunohistochemistry and western blotting. Furthermore, DCI increased the mRNA expression of IRS2, PI3K, AKT, and GLUT4, and reduced that of GSK3β in liver tissue, as demonstrated by polymerase chain reaction. Finally, DCI promoted glucose consumption in high glucose-stimulating HepG2 cells and increased the expression of IRS2 protein in HepG2 cells, as revealed by fluorescence staining and flow cytometry. Our results indicate that DCI can significantly improve glucose metabolism in diabetic mice and HepG2 cells. This effect may be associated with the upregulation of IRS2, PI3K, AKT, and GLUT4 and downregulation of GSK3β.
Highlights
Diabetes mellitus is a lifelong metabolic disease characterized by hyperglycemia, which is caused by insufficient secretion or dysfunction of insulin (Hummel et al, 1966; Rutter et al, 1999; Tian et al, 2017)
The 30 db/db mice were randomly divided into three groups receiving different treatments: high-dose DCI group (HDCIG), low-dose DCI group (LDCIG) and model control group (MCG)
Compared with MCG, daily water intake in administration groups gradually decreased with unvisible difference in daily feed intake
Summary
Diabetes mellitus is a lifelong metabolic disease characterized by hyperglycemia, which is caused by insufficient secretion or dysfunction of insulin (Hummel et al, 1966; Rutter et al, 1999; Tian et al, 2017). The incidence of diabetes is increasing annually. The prevalence of diabetes in China is approximately 11%, ranking first worldwide (Cheung et al, 2018). As one of the independent risk factors of type 2 diabetes mellitus (T2DM), insulin resistance (IR) is closely associated with various metabolic diseases (Cordain et al, 2003; Mehanna et al, 2018). IR induces various diabetic complications (e.g., diabetic liver injury) (Ji et al, 2009), which occur throughout the entire developmental process of T2DM and cause harm to diabetic patients. It is of great importance to identify effective drugs for the prevention and reduction of IR
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