Grape seed extract supplementation prevents high-fructose diet-induced insulin resistance in rats by improving insulin and adiponectin signaling pathways

Grape seed extract supplementation prevents high-fructose diet-induced insulin resistance in rats by improving insulin and adiponectin signaling pathways

e22 Abstracts B lymphocytes stimulated by LPS, AAP 400 μg/mL and AP 400 μg/mL increase the proliferation of splenocytes significantly. APS 25, 100 a...

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e22

Abstracts

B lymphocytes stimulated by LPS, AAP 400 μg/mL and AP 400 μg/mL increase the proliferation of splenocytes significantly. APS 25, 100 and 400 μg/mL showed inhibiting effect on lymphocytes. The effect of TP was not significant. Conclusion: The results indicated that the immunomodulatory effects of four polysaccharides were individually variable. AP 25, 100 and 400 μg/mL showed more evident synergistic effect combining with ConA than other polysaccharides. AP 400 μg/mL acted remarkable immunoenhancement on lymphocytes stimulated by LPS. This study implies that AP should be explored as an effective immunostimulant and therapeutic medicine. Keywords: Polysaccharides, Splenic lymphocytes, Immunoenhancement doi:10.1016/j.ejphar.2011.09.243

Grape seed extract supplementation prevents high-fructose diet-induced insulin resistance in rats by improving insulin and adiponectin signaling pathways A. Meeprom, W. Sompong, W. Suwannaphet, S. Yibchok-anun, S. Adisakwattana⁎ Chulalongkorn University, Thailand E-mail address: [email protected] (S. Adisakwattana)

Propolis is a sticky, resinous material that honey bees collect from various plants, and mix with wax and other secretions. The aim of this study was to evaluate the antidiabetic effect of propolis through an analysis of the expression and enzyme activity of glucose-6phosphatase (G6Pase) and to elucidate the mechanism by which propolis inhibits G6Pase gene expression. When HepG2 cells were incubated in high glucose media (25 mM), G6Pase expression was induced. Propolis significantly reduced the expression and enzyme activity of G6Pase; however, the hypoglycemic effect was not abolished by the phosphoinositide 3-kinase inhibitor, LY294002, and by the mitogen-activated protein kinase (MAPK) inhibitor, U0126. Propolis inhibited the activity of GSK3α and β via the inhibition of serine and tyrosine phosphorylation, specifically, Y279 for GSK3α and Y216 for GSK3β. The phosphorylations of Y279 and Y216 occur through autophosphorylation by GSK3α/β and are involved in their own activity. Although propolis showed antioxidant activity, antidiabetic effect of propolis was not influenced by hydrogen peroxide and N-acetylcysteine. These results suggest that propolis inhibits the expression of G6Pase by inhibiting the autophosphorylation of Y279 and Y216 of GSK3α and β, respectively, which are involved in the activation of GSK3. These findings suggest that propolis may be a potential antidiabetic agent for the treatment of insulin-insensitive diabetes. [This work was supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Project No. 2010-0020141) to H-J Bae]. Keywords: Glucose-6-phosphatase, Propolis, Anti-diabetics, GSK3a/b

Recent evidence strongly supports the contention that grape seed extract (GSE) improves hyperglycemia and hyperinsulinemia in high fructose-fed rats. To explore the underlying molecular mechanisms of action, we examined the effects of GSE on the muscle protein level related to the insulin signaling pathway and mRNA expression of genes involved in the adiponection signaling pathway. Compared to the rats fed on a normal diet, the fructose-fed rats developed pathological changes including insulin resistance, hyperinsulinemia, hypertriglyceridemia, and high fructosamine level. These disorders were effectively attenuated in high fructose-fed rats supplemented with GSE. High fructose diet cause insulin resistance by a significant reduction in the protein expression of IR, IRS-1, Akt, and GLUT4 and mRNA expression of adiponectin, AdipoR1, and AMPK-α in skeletal muscle. The supplementation of GSE enhanced the expression of insulin signaling pathway-related proteins, including Akt and GLUT4. GSE also increased the mRNA expression of adiponectin, AdipoR1, and AMPK-α. In addition, GSE increased the mRNA levels of glycogen synthase and suppressed the mRNA expression of GSK3-α, causing an increase in glycogen accumulation in skeletal muscle. These results suggest that GSE ameliorates the defective insulin and adiponectin signaling pathways in skeletal muscle, resulting in improvement of insulin resistance in fructose-fed rats. Keywords: Grape seed extract, Fructose, Insulin signaling, Adiponectin signaling doi:10.1016/j.ejphar.2011.09.244

Anti-diabetic effect of propolis: Reduction of expression of glucose-6- phosphatase through inhibition of Y279 and Y216 autophosphorylation of GSK-3a/β in HepG2 cells L.J. Kang, Y.J. Choi, S.G. Lee, H.J. Bae⁎ et al. Chonnam National University, Republic of Korea E-mail address: [email protected] (H.J. Bae)

doi:10.1016/j.ejphar.2011.09.245

Dietary polyunsaturated fatty acid prevents hyperlipidemia and hepatic oxidant status in gestational diabetic rats and their macrosomic offspring M. Maknia,b,⁎, M. Sefia, H. Fetouia, E. Garouia, N. Zeghala a

University of Sfax, Tunesia ISET Sidi Bouzid, Tunesia E-mail address: [email protected] (M. Makni)

b

A considerable amount of clinical and experimental evidence now exists and suggesting the involvement of fatty acids and free radical-mediated oxidative processes in the pathogenesis of diabetic complications. Foetuses from mothers with diabetes are at increased risk of developing neonatal macrosomia and oxidative stress. We investigated the modulation of antioxidant status and liver biochemical parameters in gestational normal and diabetic rats and their offspring. Animals were randomly allocated into three groups of six rats each: a control pregnant group (PCD), pregnant diabetic group (PDD) and pregnant diabetic rats fed with Flax and Sesame seeds mixture (PDLS) group. The time course of changes in lipid metabolism and antioxidant status by dietary rich in ω3 and ω6 polyunsaturated fatty acids (PUFAs) in alloxan-induced diabetic rats during pregnancy and their macrosomic offspring at birth and through weaning was studied. Glucose and insulin levels were also assessed in order to characterize the diabetic state of dams and their offspring. The diabetic rats presented a significant increase in glycemia, plasma and liver lipid parameters compared to the control group. In addition, liver malonaldialdehyde levels (MDA) significantly increased. Antioxidant enzymes activities such as catalase (CAT) and superoxide dismutase (SOD) and reduced glutathione levels (GSH) significantly decreased in the liver of diabetic rats compared to controls. Diet supplemented with Flax and Sesame seeds mixture in