Dataset Information

A Dipeptidyl Peptidase-4 Inhibitor Suppresses Macrophage Foam Cell Formation in Diabetic db/db Mice and Type 2 Diabetes Patients.

ABSTRACT: Dipeptidyl peptidase-4 (DPP-4) inhibitors could have antiatherosclerotic action, in addition to antihyperglycemic roles. Because macrophage foam cells are key components of atherosclerosis, we investigated the effect of the DPP-4 inhibitor teneligliptin on foam cell formation and its related gene expression levels in macrophages extracted from diabetic db/db (C57BLKS/J Iar -+Leprdb/+Leprdb ) mice and type 2 diabetes (T2D) patients ex vivo. We incubated mouse peritoneal macrophages and human monocyte-derived macrophages differentiated by 7-day culture with oxidized low-density lipoprotein in the presence/absence of teneligliptin (10?nmol/L) for 18 hours. We observed remarkable suppression of foam cell formation by teneligliptin treatment ex vivo in macrophages isolated from diabetic db/db mice (32%) and T2D patients (38%); this effect was accompanied by a reduction of CD36 (db/db mice, 43%; T2D patients, 46%) and acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) gene expression levels (db/db mice, 47%; T2D patients, 45%). Molecular mechanisms underlying this effect are associated with downregulation of CD36 and ACAT-1 by teneligliptin. The suppressive effect of a DPP-4 inhibitor on foam cell formation in T2D is conserved across species and is worth studying to elucidate its potential as an intervention for antiatherogenesis in T2D patients.

SUBMITTER: Terasaki M

PROVIDER: S-EPMC6304851 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Dipeptidyl Peptidase-4 Inhibitor Suppresses Macrophage Foam Cell Formation in Diabetic db/db Mice and Type 2 Diabetes Patients.

Terasaki Michishige M Hiromura Munenori M Mori Yusaku Y Kohashi Kyoko K Kushima Hideki H Koshibu Masakazu M Saito Tomomi T Yashima Hironori H Watanabe Takuya T Hirano Tsutomu T

International journal of endocrinology 20181209

Dipeptidyl peptidase-4 (DPP-4) inhibitors could have antiatherosclerotic action, in addition to antihyperglycemic roles. Because macrophage foam cells are key components of atherosclerosis, we investigated the effect of the DPP-4 inhibitor teneligliptin on foam cell formation and its related gene expression levels in macrophages extracted from diabetic db/db (C57BLKS/J Iar -+Leprdb/+Leprdb ) mice and type 2 diabetes (T2D) patients ex vivo. We incubated mouse p ...[more]

PMID: 30627161

Similar Datasets

Project description:Cardiovascular disease is the leading cause of death among those with diabetes mellitus. Vitamin D deficiency is associated with an increased risk of cardiovascular disease in this population. To determine the mechanism by which vitamin D deficiency mediates accelerated cardiovascular disease in patients with diabetes mellitus, we investigated the effects of active vitamin D on macrophage cholesterol deposition.We obtained macrophages from 76 obese, diabetic, hypertensive patients with vitamin D deficiency (25-hydroxyvitamin D <80 nmol/L; group A) and 4 control groups: obese, diabetic, hypertensive patients with normal vitamin D (group B; n=15); obese, nondiabetic, hypertensive patients with vitamin D deficiency (group C; n=25); and nonobese, nondiabetic, nonhypertensive patients with vitamin D deficiency (group D; n=10) or sufficiency (group E; n=10). Macrophages from the same patients in all groups were cultured in vitamin D-deficient or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] -supplemented media and exposed to modified low-density lipoprotein cholesterol. 1,25(OH)(2)D(3) suppressed foam cell formation by reducing acetylated or oxidized low-density lipoprotein cholesterol uptake in diabetic subjects only. Conversely, deletion of the vitamin D receptor in macrophages from diabetic patients accelerated foam cell formation induced by modified LDL. 1,25(OH)(2)D(3) downregulation of c-Jun N-terminal kinase activation reduced peroxisome proliferated-activated receptor-gamma expression, suppressed CD36 expression, and prevented oxidized low-density lipoprotein-derived cholesterol uptake. In addition, 1,25(OH)(2)D(3) suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1 expression, and prevented oxidized and acetylated low-density lipoprotein-derived cholesterol uptake.These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.

Dataset Information

A Dipeptidyl Peptidase-4 Inhibitor Suppresses Macrophage Foam Cell Formation in Diabetic db/db Mice and Type 2 Diabetes Patients.

Publications

A Dipeptidyl Peptidase-4 Inhibitor Suppresses Macrophage Foam Cell Formation in Diabetic <i>db/db</i> Mice and Type 2 Diabetes Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets