Mechanism Of Preventing Mouse From Insulin Resistance By Chlorogenic Acid

1.In this paper, methord of establishment of a Kunming mouse-model with insulin resistance was studied,30 Kunming mouse were divided into three groups with free acess to food and water, two of which were administrated with fat emulsion to induced insulin resisitance, incluing high dose of fat emulsion(HE)(a constant volume of 200 mL fat emulsion containing 20 glard,2 g thyreostat,5 g cholesterol,1 g sodium glutamate,2 g protein,10 g fructose and 5 g saccharose,20 mL Tween 80, 30 mL propylene glycol was prepared by adding distilled water)and the low dose of fat emulsion (LE) (a constant volume of 300 mL fat emulsion containing 20 glard,2 g thyreostat,5 g cholesterol,1 g sodium glutamate,2 g protein,10 g fructose and 5 g saccharose,20 mL Tween 80,30 mL propylene glycol was prepared by adding distilled water), some key physiological factors were detected and the results showed that FBG and 2h postprandial blood glucose (PBG)were significantly increased by mouse administrated with HE, while plasma TG and TC increased significantly, ISI were descended, HOMA-IR index were increased. The difference were significant (P<0.05). Above indexes suggested that mouse administrated with high dose of fat emulsion had showed clincle symptoms such as hyperlipidemia, ISI reduction, and HOMA-IR index increasing, which declared high dose of fat emulsion(HE) could induce mouse to developed into insulin resistance(IR).2. Some key enzyme genes related to IR expressed in target organs of HE mouse were appraised, the results showed that expression of G-6-Pase mRNA was up (P< 0.05) while expression of skeletal muscle GLUT4 mRNA and protein were down(P< 0.01). To determine whether high dose of fat emulsion damage kidney and pancreas or not, pathology of kidney and pancreas were analyzed, pathological changes in kidney were observed with mild glamorous hypertrophy, distance tubules expansion, mild edema proximal tubules and unclear renal interstitial etc; Further studies showed that pancreatic islets cell density decreased slightly companying nucleus shape changes, uneven cell distribution. Insulin specific immunohistochemical forβ-cell showed the average gray value ofβ-cell significantly decreased. The expression changes of key factors above related IR and pathological changes in kidney and pancreas suggested the mouse model with insulin resistance was established successfully.3. Mechanism of preventing mouse from insulin resistance by chlorogenic acid(CA) was studied, the results showed that FBG was significantly decreased (P<0.01) and 2h postprandial blood glucose(PBG) was down(P<0.05) by mouse administrated with CA, HOMA-IR index reduction(P<0.01), ISI increasing(P<0.01), plasma TG decreased significantly(P<0.01),and LDL-c was down(P<0.05). Some key enzyme genes related to IR expressed in target organs of CA mouse were detected, the results showed that expression of G-6-Pase mRNA was down while expression of skeletal muscle GLUT4 mRNA was up(P<0.01). To determine whether CA protect kidney and pancreas or not, pathology of kidney and pancreas were analyzed, pathological changes in kidney of HE mouse were observed with glomerulus hypertrophy, glomerulus basal plasmamembrane thickening. Glomerulus were diffuse with glass-like substance, renal tubular epithelial cells appeared vacuolar degeneration etc; Further studies showed that pancreatic islets cell nucleus of HE mouse were not clear. But there were no above symptoms in CA mouse. Insulin specific immunohistochemical forβ-cell showed the average gray value ofβ-cell of CA mouse significantly increased. The expression changes of key factors above related IR and pathological analysis in kidney and pancreas suggested chlorogenic acid prevented mouse from insulin resistance.