Abstract
The purpose of this study was to investigate the effects of leaf extract from Lithocarpus polystachyus Rehd. on type II diabetes mellitus (T2DM) and the active ingredients of this effect. In addition, this study determined, for the first time, the underlying molecular and pharmacological mechanisms of the extracts on hyperglycemia using long-term double high diet-fed and streptozotocin (STZ) induced type II diabetic mice. In the present study, leaf extract, phloridzin and trilobatin were assessed in vivo (gavage) and in vitro (non-invasive micro-test technique, NMT) in experimental T2DM mice. The biochemical parameters were measured including blood glucose and blood lipid level, liver biochemical indexes, and hepatic glycogen. The relative expression of glycometabolism-related genes was detected. The effect of leaf extracts on physiological glucose flux in liver tissue from control and T2DM mice was also investigated. Body weight of experimental T2DM mice increased significantly after the first week, but stabilized over the subsequent three weeks; body weight of all other groups did not change during the four weeks’ study. After four weeks, all treatment groups decreased blood glucose, and treatment with leaf extract had numerous positive effects: a) promoted in glucose uptake in liver, b) increased synthesis of liver glycogen, c) reduced oxidative stress, d) up-regulation of glucokinase (GK), glucose transporter 2 (GLUT2), insulin receptor (IR) and insulin receptor substrate (IRS) expression in liver, e) down-regulation of glucose-6-phosphatase (G-6-P) expression, and f) ameliorated blood lipid levels. Both treatment with trilobatin or phloridzin accelerated liver glycogen synthesis, decreased oxidative stress and increased expression of GK. IRS and phosphoenolpyruvate carboxykinase (PEPCK) were both up-regulated after treatment with trilobatin. Expression of GLUT2, PEPCK and G-6-P were also increased in liver tissue after treatment with phloridzin. Our data indicate that leaf extract from L. polystachyus Rehd. has a preferable hypoglycemic effects than trilobatin or phloridzin alone. Leaf extract significantly increased glucose uptake and hepatic glycogen synthesis while also inducing a decline of hepatic gluconeogenesis and oxidative stress in T2DM mice. From this study, we draw conclusions that L. polystachyus promoted glycogen synthesis in T2DM mice, and that the active compounds were not only the trilobatin or phloridzin.
Highlights
Type II diabetes mellitus (T2DM) is the third largest fatal disease, following only cancer and cardiovascular disease, and is one of the most challenging healthcare epidemics in the world [1,2]
The body weight of all groups did not change significantly, with exception of TD2M mice—which increased after the first week and stabilized over the subsequent three weeks, and trilobatin—which slightly increased at the first week and fluctuated after the continue weeks
After one-week gavage, T2DM mice, and groups of leaf extract, phloridzin and trilobatin had significantly higher blood glucose than the control group, but mice treated with glibenclamide did not
Summary
Type II diabetes mellitus (T2DM) is the third largest fatal disease, following only cancer and cardiovascular disease, and is one of the most challenging healthcare epidemics in the world [1,2]. The most common clinical manifestations of T2DM is high blood glucose levels. T2DM is a complex disorder characterized by abnormal metabolism of carbohydrates, lipids and proteins that results in the absolute or relative reduction of insulin activity [3]. Insulin resistance and pancreatic β cell dysfunction are causative factors and not the main mechanism of T2DM. Insulin signal transduction is initiated when insulin receptors (IR) are activated, providing docking sites for insulin receptor substrate (IRS) proteins that transduce insulin signaling to phosphatidylinositol (PI) 3-kinase [1]. In T2DM, plasma glucose clearance is relatively inefficient, inducing insulin resistance; within liver tissues this eventually results in altered metabolic gene expression and impaired glycometabolism [5], contributing to fasting hyperglycemia [6]. There is recent evidence that protein tyrosine phosphatase 1B (PTP1B) activity is the pathogenesis of insulin resistance [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
