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Visfatin: a new player in mesangial cell physiology and diabetic nephropathy
Hye Kyoung Song1, Mi Hwa Lee, Bo Kyung Kim
1Department of Internal Medicine, Korea University, Ansan City, Kyungki-Do, Korea.
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.
Insights
Visfatin, an adipokine, is synthesized in kidney mesangial cells and promotes glucose uptake and profibrotic molecule synthesis, contributing to diabetic nephropathy. This study reveals visfatin
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Visfatin, an adipokine, is known for its insulin-sensitizing and antidiabetic effects.
- Its role and synthesis within the kidney, particularly in diabetic nephropathy, remain largely unexplored.
Purpose of the Study:
- To investigate the synthesis and physiological actions of visfatin in cultured human mesangial cells (MCs).
- To elucidate the role of visfatin in the pathogenesis of diabetic nephropathy.
Main Methods:
- Cultured human mesangial cells were treated with visfatin under high glucose conditions.
- Glucose uptake, NAD+ levels, glucose transporter-1 (GLUT-1) expression, and profibrotic molecule synthesis were measured.
- Inhibitors and small interfering RNA targeting the insulin receptor and nicotinamide phosphoribosyltransferase (Nampt) were utilized.
Main Results:
- Visfatin is synthesized in mesangial cells, with synthesis upregulated by high glucose.
- Visfatin stimulates glucose uptake via GLUT-1 translocation and enhances intracellular NAD+ levels.
- Visfatin treatment increases the synthesis of profibrotic factors like TGF-β1, PAI-1, and collagen type I.
Conclusions:
- Mesangial cells are a novel source and target for visfatin.
- Visfatin plays a significant role in the pathogenesis of diabetic nephropathy by modulating glucose metabolism and promoting fibrosis.
