The role of sorbitol pathway and treatment effect of aldose reductase inhibitor ONO2235 in the up-regulation of cardiac M2-muscarinic receptors in streptozotocin-induced diabetic rats.
This study investigated the role of the sorbitol pathway on the genetic up-regulation of the cardiac M(2) muscarinic receptor (M(2)-mAChR) in streptozotocin (STZ)-induced diabetic rats. Three-month-old male Wistar rats were divided into five groups: (1) normal controls; (2) rats rendered diabetic by streptozotocin; (3) rats fed with glucose; (4) rats injected with sorbitol; and (5) diabetic rats treated with ONO-2235, an aldose reductase inhibitor. The M(2) muscarinic receptor (M(2)-mAChR) protein and mRNA densities of the heart tissue were measured by Western immunoblotting and Northern blotting, respectively. The densities of M(2)-mAChR protein and mRNA in the heart were significantly increased in diabetic rats, and rats given either glucose or sorbitol. When diabetic rats were treated with ONO-2235, the increases in heart M(2)-mAChR protein and mRNA were significantly reduced. The findings suggest that hyperglycemia and the sorbitol pathway are involved in the pathogenesis of diabetic heart disease in STZ-induced diabetic rats. Aldose reductase inhibitors may be useful in the treatment and prevention of cardiac complication in diabetes.
Liu
Tsang-Pai
TP
Department of General Surgery, Mackay Memorial Hospital, and Mackay Nursing College, Taipei City, Taiwan, ROC.
Juang
Shiow-Wen
SW
Cheng
Juei-Tang
JT
Tong
Yat-Ching
YC
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D005947:Glucose; D008297:Male; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013012:Sorbitol / Q000008:administration & dosage*; D013311:Streptozocin; D013549:Sweetening Agents / Q000008:administration & dosage*; D053778:Thiazolidines; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D043585:Receptor, Muscarinic M2; D013549:Sweetening Agents; D053778:Thiazolidines; C038131:epalrestat; D013012:Sorbitol; D013311:Streptozocin; D012236:Rhodanine; D000449:Aldehyde Reductase; D005947:Glucose