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-β1, 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.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 295 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2008 Nov 1 |
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Keywords
- Glucose transporter-1
- Glucose uptake
- Profibrotic molecule
- Protein kinase B
ASJC Scopus subject areas
- Physiology
- Urology
Cite this
Visfatin : A new player in mesangial cell physiology and diabetic nephropathy. / Hye, Kyoung Song; Mi, Hwa Lee; Bo, Kyung Kim; Park, Yun Gyu; Ko, Gang Jee; Kang, Young Sun; Jee, Young Han; Sang, Youb Han; Kum, Hyun Han; Hyoung, Kyu Kim; Cha, Dae-Ryong.
In: American Journal of Physiology - Renal Physiology, Vol. 295, No. 5, 01.11.2008.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Visfatin
T2 - A new player in mesangial cell physiology and diabetic nephropathy
AU - Hye, Kyoung Song
AU - Mi, Hwa Lee
AU - Bo, Kyung Kim
AU - Park, Yun Gyu
AU - Ko, Gang Jee
AU - Kang, Young Sun
AU - Jee, Young Han
AU - Sang, Youb Han
AU - Kum, Hyun Han
AU - Hyoung, Kyu Kim
AU - Cha, Dae-Ryong
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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-β1, 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.
AB - 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-β1, 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.
KW - Glucose transporter-1
KW - Glucose uptake
KW - Profibrotic molecule
KW - Protein kinase B
UR - http://www.scopus.com/inward/record.url?scp=57349120067&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57349120067&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.90231.2008
DO - 10.1152/ajprenal.90231.2008
M3 - Article
VL - 295
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 1931-857X
IS - 5
ER -