Dipeptidyl peptidase 4 inhibitor anagliptin ameliorates hypercholesterolemia in hypercholesterolemic mice through inhibition of intestinal cholesterol transport

Journal of Diabetes Investigation
Moritaka GotoKohei Kaku

Abstract

Recent data showed that dipeptidyl peptidase 4 (DPP-4) inhibitors exert a lipid-lowering effect in diabetes patients. However, the mechanism of action is not yet clearly understood. We investigated the effect of anagliptin on cholesterol metabolism and transport in the small intestine using non-diabetic hyperlipidemic animals, to clarify the mechanisms underlying the cholesterol-lowering action. Male apolipoprotein E (ApoE)-deficient mice were orally administered anagliptin in the normal chow. Serum cholesterol levels and lipoprotein profiles were measured, and cholesterol transport was assessed by measuring the radioactivity in the tissues after oral loading of 14 C-labeled cholesterol (14 C-Chol). In additional experiments, effects of exendin-4 in mice and of anagliptin in DPP-4-deficient rats were assessed. Effects on target gene expressions in the intestine were analyzed by quantitative polymerase chain reaction in normal mice. The serum total and non-high-density lipoprotein cholesterol concentrations decreased after anagliptin treatment in the ApoE-deficient mice. The cholesterol-lowering effect was predominantly observed in the chylomicron fraction. The plasma 14 C-Chol radioactivity was significantly decreased by 26% at...Continue Reading

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Citations

Jun 5, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Zhenbo ChenQinghe Yao
Oct 10, 2019·Archives of Physiology and Biochemistry·Maxim Yu SinitskyAnastasia V Ponasenko
Apr 2, 2020·Journal of Diabetes Investigation·Takashi Matsuzaka, Hitoshi Shimano
Feb 5, 2021·Obesity Surgery·Carsten T HerzGerit-Holger Schernthaner

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