Effects of glucose and insulin on expression and function of bile acid transporters in sandwich cultured rat hepatocytes

Abstract

Abstract: AIM: To explain the enhancement of bile acid excretion in diabetes from bile acid transporter perspective.METHODS: Primary rat hepatocytes were isolated and cultured in a sandwich configuration (SCRH). Then hepatocytes were cultured with different concentrations of glucose and insulin, and function of Na⁺/bile acid cotransporter (ntcp) and bile salt export pump (bsep) were tested with Cholyl-lysyl-fluorescein (CLF) as a typical substrate. mRNA levels of ntcp, bsep and lipid regulating nuclear receptor fxr were determined with Real Time PCR.RESULTS: CLF biliary excretion was both decreased in high concentrations of glucose and insulin significantly.Both high concentrations of glucose and insulin can decrease ntcp mRNA for 3-4 fold, but increase bsep mRNA for approximately 2 fold. Levels of fxr mRNA was down regulated in high concentrations of glucose and up regulated in high concentrations of insulin.CONCLUSION: Abnormal glucose and insulin concentration have impacts on bile acid transporters in sandwich cultured rat hepatocytes.Sandwich cultured rat hepatocytes could offer a useful tool to explore hepatobiliary disposition of bile acid and drugs.

Key words: Glucose, Insulin, Sandwich cultured rat hepatocyte, Bile acid transporter

CLC Number:

R965.2

HE Lei, GUO Cen, YAO Dan, SHENG Jing-jing, PAN Guo-yu, LIU Xiao-dong. Effects of glucose and insulin on expression and function of bile acid transporters in sandwich cultured rat hepatocytes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(8): 847-852.

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