title: Anti-hypertensive azelnidipine preserves insulin signaling and glucose uptake against oxidative stress in 3T3-L1 adipocytes.
abstract: It is known that reactive oxygen species (ROS) are involved in the development of insulin resistance as well as pancreatic β-cell dysfunction both of which are often observed in type 2 diabetes. In this study, we evaluated the effects of azelnidipine, a calcium channel blocker, on ROS-mediated insulin resistance in adipocytes. When 3T3-L1 adipocytes were exposed to ROS, insulin-mediated glucose uptake was suppressed, but such phenomena were not observed in the presence of azelnidipine. Phosphorylation of insulin receptor and phosphorylation of Akt were suppressed by ROS, which was mitigated by azelnidipine treatment. Activation of the JNK pathway induced by ROS was also reduced by azelnidipine. Various inflammatory cytokine levels were increased by ROS, which was also suppressed by azelnidipine treatment. In contrast, adiponectin mRNA and secreted adiponectin levels were reduced by ROS, which was refilled by azelnidipine treatment. In conclusion, azelnidipine preserves insulin signaling and glucose uptake against oxidative stress in 3T3-L1 adipocytes.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki 701-0192, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Tatsumi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashiramoto
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tawaramoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Obata
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Shimoda
authors.forename: Sumiko
authors.initials: S
authors.lastname: Hamamoto
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kanda-Kimura
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamei
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Mune
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuda
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D004095:Dihydropyridines; D007328:Insulin; D017382:Reactive Oxygen Species; D001383:Azetidinecarboxylic Acid; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; C061679:azelnidipine