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        Alpha-Lipoic Acid Inhibits Glycogen Synthesis and Modifies Glucose Metabolism and Signaling Pathways in Soleus Muscles from Healthy Rats

        Madar, Zecharia,Stark, Aliza H.,Ilan, Erez,Timar, Bracha,Borenshtein, Diana The Korean Society of Food Science and Nutrition 2002 Preventive Nutrition and Food Science Vol.7 No.2

        Alpha-lipoic acid is a known hypoglycemic agent that may be useful in the treatment of diabetes. The objective of this study was to investigate the fate of glucose in isolated muscles incubated with lipoic acid by determining its direct effects on specific metabolic and signaling pathways. Soleus muscles from healthy rats were incubated with lipoic acid in the absence or presence of insulin. Glucose transport, glycogen synthesis, glucose oxidation and lipid synthesis were determined and affects on major pathways associated with insulin signaling were evaluated. Glucose transport was not significantly altered by the addition of lipoic acid to the incubation medium. However, lipoic acid decreased glycogen synthesis in comparison to controls. Glucose oxidation was moderately increased while de-novo lipid synthesis from glucose was inhibited. Wortmannin repressed insulin stimulation of glucose incorporation into glycogen, an effect that was augmented by the combined treatment of wortmannin and lipoic acid. Basal and insulin-stimulated serine phosphorylation of Akt was not changed by the addition of lipoic acid to the incubation medium. These data show that in this in vitro model, lipoic acid did not significantly affect glucose uptake but dramatically modified pathways of glucose metabolism within muscle tissue.

      • KCI등재후보

        Alpha - Lipoic Acid Inhibits Glycogen Synthesis and Modifies Glucose Metabolism and Signaling Pathways in Soleus Muscles from Healthy Rats

        Aliza H. Stark,Erez Ilan,Bracha Timar,Diana Borenshtein,Zecharia Madar 한국식품영양과학회 2002 Preventive Nutrition and Food Science Vol.7 No.2

        Alpha-lipoic acid is a known hypoglycemic agent that may be useful in the treatment of diabetes. The objective of this study was to investigate the fate of glucose in isolated muscles incubated with lipoic acid by determining its direct effects on specific metabolic, signaling pathways. Soleus muscles from healthy rats were incubated with lipoic acid in the absence or presence of insulin. Glucose transport, glycogen synthesis, glucose oxidation, lipid synthesis were determined, affects on major pathways associated with insulin signaling were evaluated. Glucose transport was not significantly altered by the addition of lipoic acid to the incubation medium. However, lipoic acid decreased glycogen synthesis in comparison to controls. Glucose oxidation was moderately increased while de-novo lipid synthesis from glucose was inhibited. Wortmannin repressed insulin stimulation of glucose incorporation into glycogen, an effect that was augmented by the combined treatment of wortmannin, lipoic acid. Basal, insulin-stimulated serine phosphorylation of Akt was not changed by the addition of lipoic acid to the incubation medium. These data show that in this in vitro model, lipoic acid did not significantly affect glucose uptake but dramatically modified pathways of glucose metabolism within muscle tissue.

      • KCI등재

        Olive Leaf Extract as a Hypoglycemic Agent in Both Human Diabetic Subjects and in Rats

        Julio Wainstein,Tali Ganz,Mona Boaz,Yosefa Bar Dayan,Eran Dolev,Zohar Kerem,Zecharia Madar 한국식품영양과학회 2012 Journal of medicinal food Vol.15 No.7

        Olive tree (Olea europaea L.) leaves have been widely used in traditional remedies in European and Mediterranean countries as extracts, herbal teas, and powder. They contain several potentially bioactive compounds that may have hypoglycemic properties. To examine the efficacy of 500 mg oral olive leaf extract taken once daily in tablet form versus matching placebo in improving glucose homeostasis in adults with type 2 diabetes (T2DM). In this controlled clinical trial, 79 adults with T2DM were randomized to treatment with 500 mg olive leaf extract tablet taken orally once daily or matching placebo. The study duration was 14 weeks. Measures of glucose homeostasis including Hba1c and plasma insulin were measured and compared by treatment assignment. In a series of animal models, normal, streptozotocin (STZ) diabetic, and sand rats were used in the inverted sac model to determine the mechanism through which olive leaf extract affected starch digestion and absorption. In the randomized clinical trial, the subjects treated with olive leaf extract exhibited significantly lower HbA1c and fasting plasma insulin levels; however, postprandial plasma insulin levels did not differ significantly by treatment group. In the animal models, normal and STZ diabetic rats exhibited significantly reduced starch digestion and absorption after treatment with olive leaf extract compared with intestine without olive leaf treatment. Reduced digestion and absorption was observed in both the mucosal and serosal sides of the intestine. Though reduced, the decline in starch digestion and absorption did not reach statistical significance in the sand rats. Olive leaf extract is associated with improved glucose homeostasis in humans. Animal models indicate that this may be facilitated through the reduction of starch digestion and absorption. Olive leaf extract may represent an effective adjunct therapy that normalizes glucose homeostasis in individuals with diabetes.

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