pitavastatin and Hyperglycemia

The present study was undertaken to compare the efficacy of pitavastatin and colestimide in patients with diabetes mellitus complicated by hyperlipidemia and metabolic syndrome. 48 diabetic patients with metabolic syndrome were randomly assigned to a pitavastatin group or colestimide group. The clinical parameters, serum lipids, fasting (FPG) and postprandial plasma glucose(PPG), HOMA-IR, hemoglobin A1c(HbA1c), hs-CRP and urinary albumin were measured before/after 24-week administration. Treatment with pitavastatin reduced LDL-C and TG, while that with colestimide significantly reduced waist circumference, BMI, LDL-C, HbA1c, FPG, PPG, HOMA-R , hs-CRP and urinary albumin. Percent improvement in LDL-C was greater in the pitavastatin group than in the colestimide group. Colestimide appeared to be useful in the management of Japanese patients with diabetes mellitus complicated by metabolic syndrome, since it alleviates obesity and insulin resistance in addition to exhibiting lipid profile-improving effects, and can thus improve markers of atherosclerosis.

Topics: Adult; Aged; Albuminuria; Atherosclerosis; Biomarkers; C-Reactive Protein; Cholesterol, LDL; Diabetes Complications; Epichlorohydrin; Female; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperglycemia; Hyperlipidemias; Hypolipidemic Agents; Imidazoles; Insulin Resistance; Japan; Male; Metabolic Syndrome; Middle Aged; Obesity; Quinolines; Resins, Synthetic; Triglycerides; Weight Loss

Blood-brain barrier (BBB) disruptions are a key feature of hyperglycemia (HG)-induced cerebral damage. Patients with diabetes mellitus often have other cerebrovascular disease risk factors including hypertension, dyslipidemia, arrhythmia, and atherosclerosis obliterans. However, whether the drugs for these comorbidities are effective for improving HG-induced BBB damage is unclear.. We investigated the effect of pitavastatin, candesartan, cilostazol, propranolol, and eicosapentaenoic acid on HG-induced BBB damage. In vitro BBB models consisting of primary cultures of rat brain capillary endothelial cells were subjected to HG (55 mM d-glucose).. We observed a significant decrease in transendothelial electrical resistance (TEER) with HG, showing that HG compromised the integrity of the in vitro BBB model. No significant decrease in cell viability was seen with HG, but HG increased the production of reactive oxygen species. Pitavastatin and candesartan inhibited decreases in TEER induced by HG.. In summary, pitavastatin and candesartan improved HG-induced BBB damage and this in vitro model of HG-induced BBB dysfunction contributes to the search for BBB protective drugs.

Topics: Animals; Benzimidazoles; Biphenyl Compounds; Blood-Brain Barrier; Cilostazol; Disease Models, Animal; Eicosapentaenoic Acid; Electric Impedance; Hyperglycemia; Propranolol; Quinolines; Rats; Rats, Wistar; Reactive Oxygen Species; Tetrazoles

Podocytes form the essential components of the glomerular filtration barrier and play a critical role in diabetic nephropathy. Recent evidence suggests that HMG-CoA reductase inhibitors (statins) exert renoprotective effects. We investigated whether pitavastatin directly suppresses hyperglycaemia-induced podocyte injury using cultured podocytes and, if so, the mechanism of the beneficial effects. Cultured podocytes were exposed to media containing normal (NG; 5 mmol/L) or high (HG; 25 mmol/L) glucose for 1 week. HG increased the lethal injury of podocytes and disruption of F-actin fibers, and reduced the mRNA expression of novel podocyte markers, synaptopodin and Wilms tumor-1 (WT-1), in association with decreased bone morphogenetic protein-7 (BMP-7) expression. Pitavastatin (100 nmol/L) reduced podocyte injury and restored the mRNA expression of synaptopodin and WT1; however, these protective effects were abolished by BMP-7 siRNA. Additionally, pitavastatin suppressed HG-induced Rho kinase activation, as assessed by the phosphorylation level of myosin phosphatase targeting subunit 1 (MYTP1), and C3 exotoxin, a Rho inhibitor, mimicked the effect of pitavastatin on BMP-7 preservation. Pitavastatin attenuates hyperglycaemia-induced podocyte injury via Rho-Rho kinase-dependent BMP-7 preservation.

Topics: Animals; Apoptosis; Bone Morphogenetic Protein 7; Cell Culture Techniques; Cells, Cultured; Glucose; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperglycemia; Mice; Podocytes; Quinolines