Lipoprotein Lipase Activator NO-1886 Ameliorates Disorders Of Glucose And Lipid Metabolism And Alleviates Renal Fibrosis In Type 2 Diabetic Minipigs

Background and the aim Studies have identified that the coexistence of hyperglycemia and dyslipidemia exerts a nephrotoxic effect on type 2 diabetic patients. Hypertriglyceridemia contributes to the independent risk of diabetic nephropathy (DN), and it is significant to develop potential drugs for reducing plasma triglyceride (TG) to the treatment of DN. The novel compound NO-1886 is an activator to lipoprotein lipase (LPL), which is a key enzyme that catalyses the hydrolysis of the triacylglycerol component of circulating chylomicrons (CM) and very low density lipoproteins (VLDL). NO-1886 accelerates the expression of LPL mRNA in adipose tissue, cardiac muscle and skeletal muscle, increases the LPL protein mass and activity in plasma, thereby reducing plasma TG level and elevating plasma high density lipoprotein cholesterol (HDL-C) level. However, although NO-1886 has been proven to be highly effective in improving the chronic metabolic disorders of lipid and glucose, and in alleviating insulin resistance, the effect of NO-1886 on diabetic nephropathy in type 2 diabetes has not been elucidated.The aim of this study was â‘  to establish a humanoid animal model of type 2 diabetic nephropathy induced by a high-fat/high-sucrose/high-cholesterol diet in Guangxi Bama minipigs; â‘¡ to investigate the effects of NO-1886 on glucose and lipid metabolism disorders, and on the functional and morphological changes in minipig kidneys; â‘¢ to research the effects of NO-1886 on renal fibrosis..Materials and methods Fifteen male Guangxi Bama miniature pigs were randomized into three groups with similar body weight [n=5 in the normal control diet (CD) group; n=5 in the high-fat/high-sucrose/high-cholesterol diet (HFSCD) group;...