title: The Loss of Myocardial Benefit following Ischemic Preconditioning Is Associated with Dysregulation of Iron Homeostasis in Diet-Induced Diabetes.
abstract: Whether the diabetic heart benefits from ischemic preconditioning (IPC), similar to the non-diabetic heart, is a subject of controversy. We recently proposed new roles for iron and ferritin in IPC-protection in Type 1-like streptozotocin-induced diabetic rat heart. Here, we investigated iron homeostasis in Cohen diabetic sensitive rat (CDs) that develop hyperglycemia when fed on a high-sucrose/low-copper diet (HSD), but maintain normoglycemia on regular-diet (RD). Control Cohen-resistant rats (CDr) maintain normoglycemia on either diet. The IPC procedure improved the post-ischemic recovery of normoglycemic hearts (CDr-RD, CDr-HSD and CDs-RD). CDs-HSD hearts failed to show IPC-associated protection. The recovery of these CDs-HSD hearts following I/R (without prior IPC) was better than their RD controls. During IPC ferritin levels increased in normoglycemic hearts, and its level was maintained nearly constant during the subsequent prolonged ischemia, but decayed to its baseline level during the reperfusion phase. In CDs-HSD hearts the baseline levels of ferritin and ferritin-saturation with iron were notably higher than in the controls, and remained unchanged during the entire experiment. This unique and abnormal pattern of post-ischemic recovery of CDs-HSD hearts is associated with marked changes in myocardial iron homeostasis, and suggests that iron and iron-proteins play a causative role/s in the etiology of diabetes-associated cardiovascular disorders.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem, Israel.|Department of Otolaryngology-Head and Neck Surgery, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vinokur
authors.affiliation: The Diabetes Unit, Department of Internal Medicine, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weksler-Zangen
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Eduard
authors.initials: E
authors.lastname: Berenshtein
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Eliashar
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Mordechai
authors.initials: M
authors.lastname: Chevion
mesh_terms: D000818:Animals; D003300:Copper / Q000172:deficiency; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000209:etiology / Q000378:metabolism*; D004040:Dietary Carbohydrates / Q000009:adverse effects; D005293:Ferritins / Q000378:metabolism; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats
chemical_list: D004040:Dietary Carbohydrates; D003300:Copper; D005293:Ferritins; D007501:Iron