Ursolic acid and luteolin-7-glucoside improves rat plasma lipid profile and increases liver glycogen content through glycogen synthase kinase-3

In the present study, two phytochemicals - ursolic acid (UA) and luteolin-7-glucoside (L7G) - were assessed in vivo in healthy rats regarding effects on plasma glucose and lipid profile (total cholesterol, HDL and LDL), as well as liver glycogen content, in view of their importance in the aetiology of diabetes and associated complications. Both UA and L7G significantly decreased plasma glucose concentration. UA also significantly increased liver glycogen levels accompanied by phosphorylation of glycogen synthase kinase-3 (GSK3). The increase in glycogen deposition induced by UA (mediated by GSK3) could have contributed to the lower plasma glucose levels observed. Both compounds significantly lowered total plasma cholesterol and low-density lipoprotein levels, and, in addition, UA increased plasma high-density lipoprotein levels. Our results show that UA particularly may be useful in preventable strategies for people at risk of developing diabetes and associated cardiovascular complications by improving plasma glucose levels and lipid profile, as well as by promoting liver glycogen deposition.MFA and CMS were supported by the Foundation for Science and Technology, Portugal, through the grants SFRH/BD/12527/2003 and SFRH/BD/42566/2007, respectively. This work was supported by the Foundation for Science and Technology, Portugal, research grant POCI/AGR/62040/2004

Does green tea affect postprandial glucose, insulin and satiety in healthy subjects: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Results of epidemiological studies have suggested that consumption of green tea could lower the risk of type 2 diabetes. Intervention studies show that green tea may decrease blood glucose levels, and also increase satiety. This study was conducted to examine the postprandial effects of green tea on glucose levels, glycemic index, insulin levels and satiety in healthy individuals after the consumption of a meal including green tea.</p> <p>Methods</p> <p>The study was conducted on 14 healthy volunteers, with a crossover design. Participants were randomized to either 300 ml of green tea or water. This was consumed together with a breakfast consisting of white bread and sliced turkey. Blood samples were drawn at 0, 15, 30, 45, 60, 90, and 120 minutes. Participants completed several different satiety score scales at the same times.</p> <p>Results</p> <p>Plasma glucose levels were higher 120 min after ingestion of the meal with green tea than after the ingestion of the meal with water. No significant differences were found in serum insulin levels, or the area under the curve for glucose or insulin. Subjects reported significantly higher satiety, having a less strong desire to eat their favorite food and finding it less pleasant to eat another mouthful of the same food after drinking green tea compared to water.</p> <p>Conclusions</p> <p>Green tea showed no glucose or insulin-lowering effect. However, increased satiety and fullness were reported by the participants after the consumption of green tea.</p> <p>Trial registration number</p> <p>NCT01086189</p

Rapamycin Potentiates Transforming Growth Factor β-Induced Growth Arrest in Nontransformed, Oncogene-Transformed, and Human Cancer Cells

Transforming growth factor β (TGF-β) induces cell cycle arrest of most nontransformed epithelial cell lines. In contrast, many human carcinomas are refractory to the growth-inhibitory effect of TGF-β. TGF-β overexpression inhibits tumorigenesis, and abolition of TGF-β signaling accelerates tumorigenesis, suggesting that TGF-β acts as a tumor suppressor in mouse models of cancer. A screen to identify agents that potentiate TGF-β-induced growth arrest demonstrated that the potential anticancer agent rapamycin cooperated with TGF-β to induce growth arrest in multiple cell lines. Rapamycin also augmented the ability of TGF-β to inhibit the proliferation of E2F1-, c-Myc-, and (V12)H-Ras-transformed cells, even though these cells were insensitive to TGF-β-mediated growth arrest in the absence of rapamycin. Rapamycin potentiation of TGF-β-induced growth arrest could not be explained by increases in TGF-β receptor levels or rapamycin-induced dissociation of FKBP12 from the TGF-β type I receptor. Significantly, TGF-β and rapamycin cooperated to induce growth inhibition of human carcinoma cells that are resistant to TGF-β-induced growth arrest, and arrest correlated with a suppression of Cdk2 kinase activity. Inhibition of Cdk2 activity was associated with increased binding of p21 and p27 to Cdk2 and decreased phosphorylation of Cdk2 on Thr(160). Increased p21 and p27 binding to Cdk2 was accompanied by decreased p130, p107, and E2F4 binding to Cdk2. Together, these results indicate that rapamycin and TGF-β cooperate to inhibit the proliferation of nontransformed cells and cancer cells by acting in concert to inhibit Cdk2 activity