ABSTRACT
BACKGROUND AND OBJECTIVE: Insulin resistance is well known to exhibit essential effects on the progression of diabetes mellitus (DM). Guava leaf was also reported to exhibit anti-diabetic effects including decreasing blood glucose. Therefore, this present study aims to explore the role guava leaf extract (GLE) plays in insulin resistance and its mechanism of action via the PI3K/Akt signaling pathway. METHODS: KK-Ay mice is a spontaneous genetic type 2 diabetes mouse model induced by feeding a high fat and high sugar diet. Mice were randomly assigned into three groups: diabetic mice (DM), DM + MET (diabetic mice treated with metformin) and DM + GLE (diabetic mice treated with GLE) groups. After 8 weeks of treatment, body weight and levels of fasting plasma glucose (FPG), fasting insulin and lipids in plasma were measured. Mice were sacrificed and mRNA and protein expression of insulin receptor substrate1 (IRS1), phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase protein B (Akt) in livers were measured. RESULTS: GLE markedly reduced body weight, FPG, fasting insulin and insulin resistance index but increased the insulin sensitivity index of diabetic KK-Ay mice. Moreover, GLE upregulated the expression of IRS-1, PI3K and Akt mRNAs in livers of diabetic KK-Ay mice. In addition, GLE also elevated IRS-1, PI3K, Akt, p-PI3K and p-Akt protein expression in their livers. The results of the DM + MET group were similar to those of the DM + GLE group. CONCLUSION: GLE plays anti-diabetic roles by ameliorating insulin resistance in KK-Ay diabetic mice and this is related to the activation of PI3K/Akt signaling pathway.
ABSTRACT
OBJECTIVES: High triglycerides and low high density lipoprotein cholesterol are important cardiovascular risk factors. Triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) has been reported to be useful in predicting cardiovascular disease. Brachial-ankle pulse wave velocity (baPWV) is a valid and reproducible measurement by which to assess arterial stiffness and a surrogate marker of atherosclerosis. However, there is limited evidence about the relationship between them. Therefore, we tested the hypotheses that TG/HDL-C is associated with baPWV in healthy individuals. METHODS: Fasting lipid profiles, baPWV and clinical data were measured in 1498 apparently healthy, medication-free subjects (926 men, 572 women) who participated in a routine health screening from 2011 to 2013. Participants were stratified into quartiles of TG/HDL-C ratio. BaPWV > 1400 cm/s was defined as abnormal baPWV, Multivariable logistic regression was used to identify associations of TG/HDL-C quartiles and baPWV, after adjusting for the presence of conventional cardiovascular risk factors. RESULTS: In both genders, we observed positive relationships between TG/HDL-C quartiles and BMI, systolic BP, diastolic BP, fasting glucose, total cholesterol, LDL-C, triglycerides, uric acid, and percentages of high baPWV. Multivariable logistic regression revealed that baPWV abnormality OR value of the highest TG/HDL-C quartiles was 1.91 (95% CI: 1.11-3.30, P < 0.05) and 2.91 (95% CI: 1.02-8.30, P < 0.05) in male and female after adjusting for age, systolic BP, diastolic BP, BMI, fasting plasma glucose, LDL-C, uric acid and estimated glomerular filtration rate when compared with the lowest TG/HDL-C quartiles. CONCLUSION: Increased TG/HDL-C was independently associated with baPWV abnormality in apparently healthy individuals.
ABSTRACT
OBJECTIVE: To investigate the effect of TIEG-siRNA on Smad2, p-smad2 and collagen IV in diabetic nephropathy rats induced by streptozotocin (STZ). METHODS: Ten Sprague-Dawley rats injected with STZ were randomly divided into TIEG-siRNA and Control groups. Other five normal rats were used as control. Each of the TIEG-siRNA and Control groups were injected with TIEG-siRNA and Control 0.5 ml via tail vein at 0 and 72 hours respectively. All rats were sacrificed at week 4 after a successful modeling. To confirmed the efficacy of TIEG-siRNA in rat kidney, the TIEG levels were determined by fluorescence quantitative PCR. The expressions of Smad2, p-smad2 and collagen IV protein were detected by immunohistochemical method while Smad2 and p-smad2 examined by Western blot. RESULTS: The TIEG levels were greatly down-regulated in the TIEG-siRNA treated group (0.0636 ± 0.0066) versus the empty vector treated group (0.1054 ± 0.0111) (P < 0.05). The immunohistochemical semi-quantitative method indicated that there was a decrease in the TIEG-siRNA treated group versus the empty vector treated group: (2.13 ± 0.19)% vs (2.53 ± 0.34)% in Smad2, (21.77 ± 2.00)% vs (27.03 ± 2.51)% in p-smad2 and (3.67 ± 0.42)% vs (4.85 ± 0.43)% in collagen IV. Western blot also showed that smad2 in the TIEG-siRNA treated group (0.32 ± 0.09) was much lower than that in the empty vector treated group (0.50 ± 0.04). And p-smad2 in the TIEG-siRNA treated group (0.16 ± 0.01) was much lower than that in the empty vector treated group (0.32 ± 0.02) (P < 0.05). CONCLUSION: TIEG-siRNA may be useful in preventing the progression of diabetic nephropathy through influencing the expression of Smad2 and its activation and down-regulating collagen IV.
