Insulin induces proliferation and cardiac differentiation of P19CL6 cells in a dose-dependent manner.

Insulin is a peptide hormone produced by beta cells of the pancreas. The roles of insulin in energy metabolism have been well studied, with most of the attention focused on glucose utilization, but the roles of insulin in cell proliferation and differentiation remain unclear. In this study, we observed for the first time that 10 nmol/L insulin treatment induces cell proliferation and cardiac differentiation of P19CL6 cells, whereas 50 and 100 nmol/L insulin treatment induces P19CL6 cell apoptosis and blocks cardiac differentiation of P19CL6 cells. By using real-time polymerase chain reaction (PCR) and Western blotting analysis, we found that the mRNA levels of cyclin D1 and α myosin heavy chain (α-MHC) are induced upon 10 nmol/L insulin stimulation and inhibited upon 50/100 nmol/L insulin treatment, whereas the mRNA levels of BCL-2-antagonist of cell death (BAD) exists a reverse trend. The similar results were observed in P19CL6 cells expressing GATA-6 or peroxisome proliferator-activated receptor α (PPARα). Our results identified the downstream targets of insulin, cyclin D1, BAD, α-MHC, and GATA-4, elucidate a novel molecular mechanism of insulin in promoting cell proliferation and differentiation.

Lack of association between SLCO1B1 polymorphism and the lipid-lowering effects of atorvastatin and simvastatin in Chinese individuals.

PURPOSE: There is significant inter-individual variability in the lipid-lowering effects of atorvastatin and simvastatin. Our goal was to investigate the impact of SLCO1B1 genetic polymorphism on the lipid-lowering effects of atorvastatin and simvastatin. METHODS: We recruited 363 unrelated hyperlipidemic patients with the CYP3A4 1/1, CYP3A5 1/1, and CYP3AP1 1/1 genotypes: 189 of these were treated with atorvastatin and 174 were treated with simvastatin as a single-agent therapy (20 mg day(-1) orally) for 4 weeks. The genotyping of SLCO1B1 c.521T > C (p.V174A, OATP-C5) was performed with allele-specific polymerase chain reaction (AS-PCR), and PCR restriction fragment length polymorphism (RFLP) was performed to detect the carriers of SLCO1B1 c.388A > G (p.N130D, OATP-C1b). Serum triglyceride (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were determined before and after treatment. RESULTS: The frequencies of the SLCO1B1 521T > C and 388A > G variant alleles in Chinese hyperlipidemic patients were found to be 16.2% and 72.1% respectively. After treatment with 20 mg simvastatin or atorvastatin daily for 4 weeks, TC, TG, and LDL-C concentrations were lower than at baseline, on average, by 18.1 ± 3.7%, 25.8 ± 9.7%, 27.7 ± 5.4% in the simvastatin-treated group, and 17.5 ± 3.7%, 22.6 ± 8.6%, 27.5 ± 5.5% in the atorvastatin-treated group respectively, and the mean relative reduction in serum HDL cholesterol did not reach statistical significance (-1.0 ± 10.9%, 0.5 ± 9.3%). However, no significant differences were observed in the lipid-lowering effects of atorvastatin and simvastatin between subjects with different SLCO1B1 genotypes. CONCLUSION: The SLCO1B1 521T > C and 388A > G variants were found to be relatively common in Chinese patients with essential hyperlipidemia. These frequencies were found to be similar to those observed in healthy Chinese and Japanese individuals, but significantly different from Caucasians and blacks. SLCO1B1 521T > C and 388A > G polymorphisms may not be associated with the lipid-lowering effects of atorvastatin and simvastatin.

Effects of combination therapy with perindopril and losartan on left ventricular remodelling in patients with myocardial infarction.

1. Inhibiting the renin-angiotensin-aldosterone system prevents left ventricular (LV) remodelling after myocardial infarction (MI). 2. The present study was designed to assess the effects of a combination of perindopril and losartan on LV remodelling, cardiac function and serum procollagen type III amino terminal peptide (PIIINP) levels in patients with acute MI. 3. Patients with anterior MI were divided into three groups: (i) MI + perindopril; (ii) MI + losartan; and (iii) MI + perindopril + losartan. After successful intervention therapy, perindopril (2-4 mg daily), losartan potassium (25-50 mg daily) or their combination were administered. All patients received aspirin, clopidogrel and statins, and some patients were given beta-blockers, nitrate and a platelet glycoprotein IIb/IIIa receptor antagonist. Three months later, LV dimensions and LV ejection fraction (LVEF) were measured by ultrasonography. Plasma B-type natriuretic peptide (BNP), serum C-reactive protein (CRP) and PIIINP levels were evaluated using enzyme-linked immunosorbent assay or radioimmunoassay. 4. The baseline characteristics of the three groups were the same. Three months after the initiation of therapy, all patients showed decreased CRP, increased BNP and PIIINP levels and LV dilation and dysfunction. Compared with the two monotherapy groups, patients in the combination group showed significantly lower CRP, BNP and PIIINP levels, less LV dilation and higher LVEF. Serum PIIINP levels were positively correlated with CRP levels (r = 0.597; P < 0.01) and LV end-diastolic volume index (r = 0.543; P < 0.01) and were negatively correlated with LVEF (r = -0.565; P < 0.01). 5. For patients with acute MI, combination treatment with perindopril and losartan significantly inhibited LV remodelling and improved LV function. Inhibition of myocardial interstitial fibrosis may be part of the underlying mechanism.