Cilostazol, a phosphodiesterase inhibitor, reduces microalbuminuria in the insulin-resistant Otsuka Long-Evans Tokushima Fatty rat.
We evaluated association between hyperinsulinemia/insulin resistance and microalbuminuria in the insulin-resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rat. OLETF rats showed glomerular hyperfiltration (an increase in creatinine clearance and a decrease in fractional excretion of Na) and microalbuminuria at the insulin-resistant prediabetic stage, and both were related to expression of transforming growth factor (TGF)-beta(1) and extracellular matrix protein such as fibronectin and collagen (a(1)) IV. Cilostazol, a selective type III cyclic nucleotide phosphodiesterase (PDE) inhibitor, normalized glomerular hyperfiltration and microalbuminuria with a parallel decline of TGF-beta(1) and extracellular matrix protein mRNA expression. Cilostazol may be beneficial to lessen early glomerular nephropathy in a state of hyperinsulinemia/insulin resistance.
Tohma
Takeshi
T
Second Department of Internal Medicine, University of Ryukyus, Okinawa 903-0215, Japan.
Shimabukuro
Michio
M
Oshiro
Yoshito
Y
Yamakawa
Munesada
M
Shimajiri
Yoshinori
Y
Takasu
Nobuyuki
N
D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000077407:Cilostazol; D024042:Collagen Type I / Q000097:blood; D003928:Diabetic Nephropathies / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D005353:Fibronectins / Q000097:blood; D006946:Hyperinsulinism / Q000378:metabolism*; D007333:Insulin Resistance; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D020334:Rats, Inbred OLETF; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1
D001786:Blood Glucose; D024042:Collagen Type I; D005353:Fibronectins; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000077407:Cilostazol