title: Visfatin: a new player in mesangial cell physiology and diabetic nephropathy.
abstract: Visfatin is an adipocytokine that improves insulin resistance and has an antidiabetic effect. However, the role of visfatin in the kidney has not yet been reported. In this experiment, the synthesis and physiological action of visfatin in cultured mesangial cells (MCs) were studied to investigate the role of visfatin in diabetic nephropathy. Visfatin was found synthesized in MCs as well as adipocytes. Visfatin synthesis was markedly increased, not by angiotensin II, but by high glucose stimuli. In addition, visfatin treatment induced a rapid uptake of glucose, peaking at 20 min after visfatin treatment in a dose-dependent manner. A small inhibiting RNA against insulin receptor significantly blocked visfatin-mediated glucose uptake. Visfatin stimuli also enhanced intracellular NAD levels, and treatment with FK866, which is a specific inhibitor of nicotinamide phosphoribosyltransferase (Nampt), significantly inhibited visfatin-induced NAD synthesis and glucose uptake. Visfatin treatment increased glucose transporter-1 (GLUT-1) protein expression in isolated cellular membranes, and pretreatment with cytochalasin B completely inhibited visfatin-induced glucose uptake. Moreover, immunofluorescent microscopy showed the migration of cytosolic GLUT-1 into cellular membranes after visfatin treatment. In accordance with these results, the activation of protein kinase B was detected after visfatin treatment. Furthermore, visfatin treatment dramatically increased the synthesis of profibrotic molecules including transforming growth factor-beta1, plasminogen activator inhibitor-1, and type I collagen, and pretreatment with cytochalasin B completely inhibited visfatin-induced upregulation of profibrotic molecules. These results suggest that visfatin is produced in MCs, which are a novel target for visfatin, and play an important role in the pathogenesis of diabetic nephropathy.
authors.affiliation: Department of Internal Medicine, Korea University, Ansan City, Kyungki-Do, Korea.
authors.forename: Hye Kyoung
authors.initials: HK
authors.lastname: Song
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Lee
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Kim
authors.forename: Yun Gyu
authors.initials: YG
authors.lastname: Park
authors.forename: Gang Jee
authors.initials: GJ
authors.lastname: Ko
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Kang
authors.forename: Jee Young
authors.initials: JY
authors.lastname: Han
authors.forename: Sang Youb
authors.initials: SY
authors.lastname: Han
authors.forename: Kum Hyun
authors.initials: KH
authors.lastname: Han
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Cha