title: Increase of ATP-sensitive potassium (K(ATP)) channels in the heart of type-1 diabetic rats.
abstract: BACKGROUND
  An impairment of cardiovascular function in streptozotocin (STZ)-diabetic rats has been mentioned within 5 days-to-3 months of induction. ATP-sensitive potassium (K(ATP)) channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac K(ATP) channels in diabetic disorders.
  
  
  METHODS
  Streptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr) were used to examine the effect of hyperglycemia on cardiac function and the expression of K(ATP) channels. K(ATP) channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of K(ATP) channels by Western blot and Northern blot analysis.
  
  
  RESULTS
  The result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of K(ATP) channel. Two subunits of cardiac K(ATP) channel (SUR2A and kir 6.2) were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac K(ATP) in these diabetic rats.
  
  
  CONCLUSIONS
  Both mRNA and protein expression of cardiac K(ATP) channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some K(ATP) channel drugs.
authors.affiliation: Department of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan City 73101, Taiwan.
authors.forename: Zhih-Cherng
authors.initials: ZC
authors.lastname: Chen
authors.forename: Yung-Ze
authors.initials: YZ
authors.lastname: Cheng
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Chen
authors.forename: Kai-Chun
authors.initials: KC
authors.lastname: Cheng
authors.forename: Yin- Xiao
authors.initials: Y
authors.lastname: Li
authors.forename: Juei- Tang
authors.initials: J
authors.lastname: Cheng
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016166:Free Radical Scavengers / Q000494:pharmacology; D006339:Heart Rate; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D054086:KATP Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism; D013311:Streptozocin; D064233:Sulfonylurea Receptors; D013997:Time Factors; D015854:Up-Regulation; D000099161:Kcnj11 Channel
chemical_list: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D003981:Diazoxide; D016166:Free Radical Scavengers; D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D010695:Phlorhizin; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D011955:Receptors, Drug; D013311:Streptozocin; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel