Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase / 中国天然药物

AIM@#To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects.@*METHOD@#HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a (GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β (IRβ), protein kinase B (also known as Akt), and glycogen synthase kinase-3β (GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet (HFD).@*RESULTS@#The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content.@*CONCLUSION@#The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.

Effects of Dietary Fatty Acid Composition on Pro -and Macro -Glycogen Utilization and Resynthesis in Rat Skeletal Muscle

The purpose of this study was to investigate that the effect of dietary fatty acid composition on pro- and macro-glycogen utilization and resynthesis. The analyses were further extended for different muscle fibers (type I, type II, & type IIb ) as well as tissues (i.e., liver & heart ). Total one hundred sixty Sprague-Dawley rats were used, and rats were randomly allocated into four experimental groups :animals fed standard chow diet (n =40 ), animals fed saturated fatty acid diet (n =40 ), animals fed monounsaturated fatty acid (n =40 ), and animals fed polyunsaturated fatty acid (n =40 ). Animals in each groups were further divided into five subgroups :sacrificed at REST (n =8 ), sacrificed at immediately after 3 hr swim exercise (P-0HR, n =8 ), sacrificed at one hour after 3 hr swim exercise (P-1HR, n =8 ), sacrificed at four hour after 3 hr swim exercise (P-4HR, n =8 ), and sacrificed at twenty-four hour after 3 hr swim exercise (P-24HR, n =8 ). Soleus (type I ), red gastrocnemius (type IIa ), white gastrocnemius (type IIb ), liver, and heart were dissected out at appropriated time point from all animals, and were used for analyses of pro- & macro-glycogen concentrations. After 8 weeks of dietary interventions, there was no significant difference in body mass in any of dietary conditions (p >.05 ). After 3 hr swim exercise, blood lactate level was higher compared to resting conditions in all groups, but it was returned to resting value after 1 hr rest (p .05 ). Regardless of forms of glycogen, the highest level was observed in liver (p <.01 ), and most cases of supercompensation after 3hr exercise observed in this study were occurred in CHOW fed tissues. Except heart muscle, all tissues used in this study showed that pro- and macro-glycogen concentration was significantly decreased after 3 hr exercise. Based on these results, two conclusions were made :first, there is no different level of glycogen content in various tissues regardless of types of fatty acids consumed and second, the highest mobilization rate would be demon-strated from CHOW fed animals compare to animals that consumed any kinds of fatty acid diet if prolonged exercise is applied.

Progress in protein kinase B / 中国病理生理杂志

Protein kinase B (Akt) is a Ser/Thr kinase,which in mammals comprise three highly homologous members known as PKB?/Akt1,PKB?/Akt2 and PKB?/Akt3. PKB is activated by hormones?growth factor and extra cellular matrix. The activation occurs downstream of PI3K. PKB phosphorylates and regulates the function of many cellular protein involved in processes that include survival,apoptosis, proliferation,glycogen metabolism and cancer progression. Although many mechanisms remains to be fully characterized,the research of PKB is thought to have a useful profect.