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.

Objective To investigate the protective the effect of NO-1886 on the expression of protein kinase C in the kidneys of diabetic minipig model induced by high-sucrose and high-fat diet.Methods 15 Guangzhou minipigs aged 3 months were randomly divided into 3 groups of normal control,diabetes,diabbetes treatment,which were fed by basaldiet,high sucrose and high fat feed or with 1.0%No-1886 respectively.These minipigs were killed at the end of 5th month.Minipigs fed with high fat/high sucrose diet were treated with No-1886,and The fasting concentrations of plasma glucose,triglyceride,serum insulin and PKC were observed.Results High fat high sucrose feeding elevated fasting plasma glucose,trglyceride and serum insulin levels significantly.Supplement of No-1886 into high fat high sucrose diet induced a decrease in plasma glucose,triglyceride,insulin and PKC concentration compared with pigs fed with the sole high fat high sucrose diet.Conclusion No-1886 suppressed plasma glucose,triglyceride,insulin and PKC level.