Visfatin is upregulated in type-2 diabetic rats and targets renal cells.
Visfatin (also known as pre-B cell colony-enhancing factor) is a newly discovered adipocytokine that is preferentially produced by visceral fat and regulated by cytokines promoting insulin resistance. Here we determined its renal synthesis and physiology in a genetic model of type 2 diabetes in rats. These rats had higher levels of visfatin synthesis in both glomeruli and tubulointerstitium compared to control rats. Plasma visfatin levels were significantly increased in the early stages of diabetic nephropathy and positively correlated with body weight, fasting plasma glucose, and microalbuminuria. Interestingly, visfatin synthesis was found to occur in podocytes and proximal tubular cells, as well as in adipocytes in vitro. Further, in both renal cells, visfatin synthesis was significantly increased by high glucose in the media but not by angiotensin II. Additionally, visfatin treatment induced rapid uptake of glucose and was associated with increased translocation of GLUT-1 to the cellular membrane of both renal cell types. Furthermore, visfatin induced tyrosine phosphorylation of the insulin receptor, activated downstream insulin signaling pathways such as Erk-1, Akt, and p38 MAPK, and markedly increased the levels of TGFbeta1, PAI-1, type I collagen, and MCP-1 in both renal cells. Thus, our results suggest that visfatin is produced by renal cells and has an important paracrine role in the pathogenesis of diabetic nephropathy.
Kang
Young Sun
YS
Department of Internal Medicine, Korea University, Ansan City, Korea.
Song
Hye Kyoung
HK
Lee
Mi Hwa
MH
Ko
Gang Jee
GJ
Han
Jee Young
JY
Han
Sang Youb
SY
Han
Kum Hyun
KH
Kim
Hyoung Kyu
HK
Cha
Dae Ryong
DR
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D007668:Kidney / Q000166:cytology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000502:physiology*; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D015854:Up-Regulation
D016207:Cytokines; D054409:Nicotinamide Phosphoribosyltransferase; D005947:Glucose