title: Downregulation of the constitutively expressed Hsc70 in diabetic myocardium is mediated by insulin deficiency.
abstract: The 70 kDa heat shock protein family plays important cardiac protective roles against myocardial injuries. Reduced myocardial protection is a common feature of diabetic myocardium. This study was carried out to define the changes in the 70 kDa heat shock protein family in the myocardium in the of streptozotocin-diabetes rats, and to explore the mechanisms through which diabetes alters the abundance of Hsp70/Hsc70 in cardiac muscle. In the diabetic myocardium, the abundance of Hsc70 was significantly reduced. The abundance of Hsp70 was low in cardiac muscle and was not induced in the diabetic myocardium. Unlike Hsp60, Hsp70 and Hsc70 did not augment insulin-like growth factor-I receptor signaling in cardiac muscle cells. In cultured cardiomyocytes, insulin directly increased the abundance of Hsc70, whereas insulin could not modulate Hsp70. Treating diabetic rats with insulin restored myocardial Hsc70 level, but phlorizin treatment failed to restore myocardial Hsc70. These in vivo and in vitro studies showed that downregulation of Hsc70 in diabetic myocardium was secondary to insulin deficiency. Thus, insulin played a major role in maintaining adequate expression of Hsc70 in cardiac muscle.
authors.affiliation: Department of Medicine, Biological Chemistry, Physiology and Biophysics, Center for Diabetes Research and Treatment, University of California, Irvine, California 92697-4086, USA.
authors.forename: Harn-Shen
authors.initials: HS
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.forename: Hou-Fen
authors.initials: HF
authors.lastname: Su
authors.forename: Hong-Da
authors.initials: HD
authors.lastname: Lin
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Yang
authors.forename: Hui-Chin
authors.initials: HC
authors.lastname: Lai
authors.forename: Ruben
authors.initials: R
authors.lastname: Mestril
authors.forename: Ping H
authors.initials: PH
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015536:Down-Regulation; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D050883:HSC70 Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting / Q000379:methods; D007328:Insulin / Q000172:deficiency* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors; D014161:Transduction, Genetic
chemical_list: D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D007328:Insulin; D051269:Sodium-Glucose Transporter 1; D007334:Insulin-Like Growth Factor I; D010695:Phlorhizin; D017526:Receptor, IGF Type 1