NO-1886 Promotes Cholesterol 7α Hydroxylase And Insulin-Like Growth Factor Ⅰ Production By Sensitizing Growth Hormone Signaling Pathway

OBJECTIVE: Previous studies reported that NO-1886 is a kind of lipoprotein lipase (LPL) activator. Animal experiments have also demonstrated that the compound improved diet-induced diabetes by sensitizing insulin action and lowering plasma lipids and glucose. In this study we sought to elucidate its action and the possible mechanism on growth hormone (GH) signaling system of IGF-1 and CYP7A1.METHODS: The experiments applied HepG2 cells and Guangxi Bama minipigs as the cellular and animal models, immuno-blotting was applied as the technique of the expression of CYP7A1, signal regulatory protein a 1 (SIRPal), 8-actin and the phosphorylation of signal transducer and activator of transcription 5b (STAT5b); Radio immune assay (RIA) as the methods of GH and IGF-1 detection; RT-PCR as the method of Swine workshop cluster 3 antigen (SWC3 antigen) mRNA detection. Plasma glucose was quantified by GOD-POD method. AG 490 was used for the block agent of JAK2 signaling. Cell experiment:1. Detected the effects of NO-1886 on CYP7A1 in HepG2 cells. This included time and dose effects, dependence on medium GH and JAK2/STAT signaling system; detecting the effect on GH signaling negative regulator SIRPal.2. Detected the effects of NO-1886 on IGF-1. IGF-1 was measured as intracellular and extracellular fractions. Examine the dependence on JAK2/STAT signaling system. Animal preparation and treatment:1. Single dose of NO-1886 on plasma IGF-1 and GH of Bama minipigs: Six male Chinese Bama minipigs were randomized into 2 groups, control group was administered 5% Arabic gum via gastric tube; NO-1886 group was administered 1g/kg NO-1886 suspended in 5% Arabic gum. Blood was sampled hourly for 8 hours. Then plasma GH and IGF-1 were detected by RIA within 7 days.2. Long term effects of NO-1886 on plasma IGF-1, insulin, glucose and hepatic CYP7A1 and SWC3 antigen: Fifteen male Chinese 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...