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Objective: To investigate the effect of insulin and gliclazide therapy on endoplasmic reticulum (ER) stress and insulin sensitivity in the liver of type 2 diabetic rats., Methods: A high fat diet plus a low-dose of streptozotocin was implemented to create a type 2 diabetic rats which were randomly divided into diabetes mellitus (DM) group, insulin treatment (INS) group and gliclazide treatment (GT) group; and healthy rats were as normal control group. Diabetic rats in INS and GT groups were given neutral protamine hagedorn (NPH) insulin and gliclazide respectively for 3 weeks. Protein expression levels of immunoglobulin binding protein (Bip), spliced X-box binding protein 1 (XBP-1s), phosphorylated c-Jun on serine 73 (p-c-Jun), phosphorylated insulin receptor substrate 1 on serine 307 (p-IRS-1), and glucose-6-phosphatase (G6Pase) in liver homogenate were detected by Western blotting., Results: Compared with the normal rats, Bip and XBP-1s in the DM group were up-regulated (0.28 ± 0.07 vs 0.90 ± 0.10 for Bip; 0.41 ± 0.07 vs 0.95 ± 0.07 for XBP-1s; both P < 0.01); p-c-Jun (0.59 ± 0.18 vs 1.94 ± 0.03), p-IRS-1 (1.73 ± 0.18 vs 5.32 ± 0.22) and G6Pase(0.11 ± 0.01 vs 0.45 ± 0.01) were increased (all P values < 0.01). In the INS group, all of aforementioned changes were reversed (0.90 ± 0.10 vs 0.25 ± 0.04 for Bip; 0.95 ± 0.07 vs 0.47 ± 0.01 for XBP-1s; 1.94 ± 0.03 vs 0.50 ± 0.10 for p-c-Jun; 5.32 ± 0.22 vs 1.59 ± 0.32 for p-IRS-1; 0.45 ± 0.01 vs 0.15 ± 0.02 for G6Pase, all P values < 0.01). In the GT group, all of aforementioned changes were also attenuated (0.90 ± 0.10 vs 0.53 ± 0.02 for Bip; 0.95 ± 0.07 vs 0.78 ± 0.02 for XBP-1s; 1.94 ± 0.03 vs 1.33 ± 0.11 for p-c-Jun; 5.32 ± 0.22 vs 3.13 ± 0.02 for p-IRS-1; 0.45 ± 0.01 vs 0.25 ± 0.01 for G6Pase, all P values < 0.05). Furthermore, all of aforementioned protein levels were down-regulated more obviously in the INS group comparing to the GT group (all P values < 0.01)., Conclusions: Both insulin and gliclazide therapy could relieve ER stress and c-Jun N-terminal kinase activity and improved insulin sensitivity. The effect of insulin on Bip, XBP-1s, p-c-Jun, p-IRS-1 and G6Pase protein expressions is more obvious than that of gliclazide, which indicates besides lowering glucose, insulin might have protective effects of anti-inflammation, anti-oxidative stress or stimulation of lipid redistribution.

Objective: To investigate the effect of early insulin therapy on NF-kappaB pathway and inflammatory cytokine responses in liver of diabetic rat., Methods: NF-kappaB p65 DNA binding was assayed with ELISA-based assay kit, cytokine gene expressions were quantified with real-time PCR and phosphoenolpyruvate carboxykinase (PEPCK), NF-kappaB and inhibitor kappaB (IkappaBalpha) protein levels were assayed with Western blot. Results Compared with control, hepatic PEPCK protein level in the untreated diabetic rat increased by 40%. Early insulin and gliclazide treatment normalized PEPCK protein level. The abundance of IkappaBalpha protein was significantly decreased and nuclear NF-kappaB p65 DNA binding activity was increased in untreated diabetic rats. IkappaBalpha protein content increased and NF-kappaB p65 DNA binding decreased during early intervention treatment. mRNAs encoding IL-1beta and TNFalpha were increased, which were reduced to normal levels after insulin and gliclazide treatment., Conclusions: It is suggested that early insulin treatment inhibits NF-kappaB activity and inflammatory cytokine responses in liver that are involved in the amelioration of insulin resistance in diabetic rats. Such results might be due to indirect antiinflammatory effects of insulin thus relieving glucotoxicity and lipotoxicity in peripheral tissues.

Objective: To investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and different stage of cardiac dysfunction., Methods: 253 consecutive patients with coronary atherosclerotic heart disease were enrolled from August 2006 to February 2007. Patients were grouped according to the functional classification of New York Heart Association (NYHA). The baPWV was measured non-invasively with a VP1000 automated PWV/ABI analyzer (PWV/ABI, Colin CO. Ltd., Komaki, Japan). At the same time, BNP, EF, LAEDV and LVESV were measured in all the patients., Results: Brachial-ankle PWV was significantly correlated with cardiac function classification of NYHA (r = 0. 444, P < 0.001), BNP( r = 0.394, < 0.001) and left ventricular end diastolic volume (r = - 0.130, P < 0.05). The under area of receiver operating charachateistic (ROC) curve was 73.9%. The ROC curve demonstrated that when the value of brachial-ankle PWV was equal to or larger than 1717 cm/s (> 1717 cm/s), the sensitivity of diagnosing mild cardiac dysfunction was 72.9% and specifity 61.8%. When its value was equal to or larger than 1900 cm/s (> or = 1900 cm/s), the sensitivity and specificity were 61.5% and 81.9% respectively., Conclusion: Brachial-ankle PWV is significantly correlated to the NYHA classification of heart failure and it may be a prospective index to diagnose early stage of cardiac dysfunction.