isoquercitrin and Hyperinsulinism

Hepatic LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) regulate the clearance of plasma LDL-cholesterol (LDL-C): LDLR promotes it, and PCSK9 opposes it. These proteins also express in pancreatic β cells. Using cultured hepatocytes, we previously showed that the plant flavonoid quercetin-3-glucoside (Q3G) inhibits PCSK9 secretion, stimulated LDLR expression, and enhanced LDL-C uptake. Here, we examine whether Q3G supplementation could reverse the hyperlipidemia and hyperinsulinemia of mice fed a high-cholesterol diet, and how it affects hepatic and pancreatic LDLR and PCSK9 expression.. For 12 weeks, mice are fed a low- (0%) or high- (1%) cholesterol diet (LCD or HCD), supplemented or not with Q3G at 0.05 or 0.1% (w/w). Tissue LDLR and PCSK9 is analyzed by immunoblotting, plasma PCSK9 and insulin by ELISA, and plasma cholesterol and glucose by colorimetry. In LCD-fed mice, Q3G has no effect. In HCD-fed mice, it attenuates the increase in plasma cholesterol and insulin, accentuates the decrease in plasma PCSK9, and increases hepatic and pancreatic LDLR and PCSK9. In cultured pancreatic β cells, however, it stimulates PCSK9 secretion.. In mice, dietary Q3G could counter HCD-induced hyperlipidemia and hyperinsulinemia, in part by oppositely modulating hepatic and pancreatic PCSK9 secretion.

Topics: Animals; Cell Line, Tumor; Cholesterol, Dietary; Dietary Supplements; Gene Expression Regulation; Glucose Transporter Type 2; Hyperinsulinism; Hyperlipidemias; Hypolipidemic Agents; Insulin Resistance; Insulin-Secreting Cells; Liver; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Organ Specificity; Pancreas; Proprotein Convertase 9; Quercetin; Receptors, LDL