ABSTRACT
Objective To investigate the effects of lipoprotein lipase activator, NO-1886, on the mRNA and protein expression of glycogen synthase kinase-3β (GSK-3β) in the kidney of diet-induced diabetic minipigs. Methods Fifteen Guangxi Bama minipigs were randomized into three groups: C group (n=5, with the normal control diet), DM group (n=5, with the high-fat and high-sucrose diet), and NO-1886 group (n=5, with the high-fat and high-sucrose diet supplemented with 1.0% NO-1886). Plasma glucose, insulin, tfiglyceride (TG), oral glucose tolerant test, creatinine and blood urea nitrogen were measured monthly. Urinary samples in the morning were used for determination of microalbumin at month 0, 2, 4 and 5. The mRNA and protein expression of GSK-3β were measured by real time PCR, Western blot and immunohistochemistry in the kidneys obtained at the end of month 5. Results Compared with the C group, levels of plasma glucose, insulin, triglyceride and mieroalbuminuria were significantly increased in the DM group. The mRNA and protein expression of GSK-3β were increased in the kidneys of diabetic pigs (mRNA 0.0272±0.0052, protein 1.1600±0.0463, P<0.01) as compared with those of normal pigs (mRNA 0.0125±0.0045, protein 0.1385±0.0664). Compared with the DM group, the concentrations of plasma glucose, insulin, triglyceride and mieroalbuminuria obviously decreased in the NO-1886 group. The mRNA and protein expression of GSK-3β were decreased in the kidneys of the NO-1886 group (mRNA 0.0162±0.0019, protein 0.8429±0.0408, P<0.05) as compared with that of the DM group. Conclusion NO-1886 can improve disorders of glucose and TG metabolism and insulin resistance, and down-regulate the expression of GSK-3β in the kidneys, and protect renal function and morphologie damage in diet-induced diabetic minipigs.