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薬理と治療
Abstract
Objectives A feature of diabetic dyslipidemia is hypertriglyceridemia╱high remnant lipoproteinemia, which play an important role in occurrence of arteriosclerosis and diabetic nephropathy. We have reported that incretin reduced serum triglyceride(TG)and remnant cholesterol. This mechanism is considered to be the direct effect of incretin, that is, the decrease of chylomicron lipoprotein by suppression of apolipoprotein B48(Apo B48)synthesis via GLP-1 receptor in the small intestine. In this study we examined the effect of incretin on the expression of Apo B48 in cultured human small intestinal epithelial cells. Methods TG-rich lipoproteins were isolated from patientʼs plasma by ultracentrifugal method. Normal human small intestinal epithelial cells from Cell Systems Co. were cultured at 37℃, 5% CO2, 95% air. The cells were incubated for 24h with TG-rich lipoproteins at the concentration of 100μg╱mL. Exendin 4 (active form)and Exendin 9-39(inactive form)were added at the concentrations of 50 pmol╱L, 100 pmol╱L and 300 pmol╱L on the 2nd day of the culture. After 6 hours, total cellular RNA was obtained. Reverse transcriptase-polymerase chain reaction was performed to evaluate the expression of Apo B48, GLP-1 receptor, Apo B100 and Apobec1 mRNA as a ratio to endogenous GAPDH mRNA. Results Exendin 4 increased GLP-1 receptor mRNA expression in human small intestinal epithelial cells. In addition, Exendin 4 decreased Apo B48 mRNA expression, but did not affect Apo B100 mRNA expression. Exendin 9-39 did not affect GLP-1 receptor, Apo B 48 and Apo B 100 mRNA expression. Exendin 4 reduced Apobec 1 mRNA expression. Conclusions Incretin(GLP-1)suppresses the synthesis of Apo B48 in the small intestine. This is one mechanism by which incretin(GLP-1)reduces serum levels of triglyceride, chylomicron and remnant lipoprotein in type 2 diabetic patients.
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