TITLE

Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

AUTHOR(S)
Qing Li; Hwang, Yuying C.; Ananthakrishnan, Radha; Oates, Peter J.; Guberski, Dennis; Ramasamy, Ravichandran
PUB. DATE
January 2008
SOURCE
Cardiovascular Diabetology;2008, Vol. 7, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
We investigated the role of polyol pathway enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH) in mediating injury due to ischemia-reperfusion (IR) in Type 2 diabetic BBZ rat hearts. Specifically, we investigated, (a) changes in glucose flux via cardiac AR and SDH as a function of diabetes duration, (b) ischemic injury and function after IR, (c) the effect of inhibition of AR or SDH on ischemic injury and function. Hearts isolated from BBZ rats, after 12 weeks or 48 weeks diabetes duration, and their non-diabetic littermates, were subjected to IR protocol. Myocardial function, substrate flux via AR and SDH, and tissue lactate:pyruvate (L/P) ratio (a measure of cytosolic NADH/NAD+), and lactate dehydrogenase (LDH) release (a marker of IR injury) were measured. Zopolrestat, and CP-470,711 were used to inhibit AR and SDH, respectively. Myocardial sorbitol and fructose content, and associated changes in L/P ratios were significantly higher in BBZ rats compared to non-diabetics, and increased with disease duration. Induction of IR resulted in increased ischemic injury, reduced ATP levels, increases in L/P ratio, and poor cardiac function in BBZ rat hearts, while inhibition of AR or SDH attenuated these changes and protected hearts from IR injury. These data indicate that AR and SDH are key modulators of myocardial IR injury in BBZ rat hearts and that inhibition of polyol pathway could in principle be used as a therapeutic adjunct for protection of ischemic myocardium in Type 2 diabetic patients.
ACCESSION #
55716393

 

Related Articles

  • Neutrophil-Mediated Injury May Play a Role in the Increased Severity of Myocardial Infarction in the ZDF Model of Type 2 Diabetes. La Bonte, Laura R.; Davis-Gorman, Grace; Stahl, Gregory L.; McDonagh, Paul F. // Diabetes;Jun2007 Supplement 1, Vol. 56, pA320 

    Diabetic patients have significantly more severe and fatal heart attacks than non-diabetic patients. In fact, cardiovascular disease is the leading cause of death among people with diabetes, accounting for two-thirds to three-fourths of all diabetes-related deaths. Inflammation may exacerbate...

  • The pleiotropic effects of metformin: time for prospective studies. Bromage, Daniel I.; Yellon, Derek M. // Cardiovascular Diabetology;Aug2015, Vol. 14 Issue 1, p1 

    The global prevalence of diabetes has risen to epidemic proportions and the trend is predicted to continue. The consequent burden of cardiovascular morbidity and mortality is a major public health concern and new treatments are required to mitigate the deleterious effects of cardiovascular...

  • DIAD: Outcome not affected by routine screening for CAD in patients with diabetes. Haigh, Christen; Kalvaitis, Katie; Raible, Eric; Southall, Jennifer // Endocrine Today;May2009, Vol. 7 Issue 7, p16 

    The article reports on a study presented at a press briefing held by the "Journal of the American Medical Association" in Washington, D. C. which showed that screening patients with type 2 diabetes for inducible ischemia was not able to identify patients who were at greater risk than others.

  • Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes. Korkmaz-Icöz, Sevil; Lehner, Alice; Li, Shiliang; Vater, Adrian; Radovits, Tamás; Hegedűs, Péter; Ruppert, Mihály; Brlecic, Paige; Zorn, Markus; Karck, Matthias; Szabó, Gábor // Journal of Diabetes Research;7/1/2015, Vol. 2015, p1 

    Despite clinical studies indicating that diabetic hearts are more sensitive to ischemia/reperfusion injury, experimental data is contradictory. Although mild diabetes prior to ischemia/reperfusion may induce a myocardial adaptation, further research is still needed. Nondiabetic Wistar (W) and...

  • Endothelial Factors and Diabetic Nephropathy. KARALLIEDDE, JANAKA; GNUDI, LUIGI // Diabetes Care;May2011 Supplement 2, Vol. 34, pS291 

    The article examines the link between endothelial dysfunction and diabetic nephropathy. Since 1996, the annual incidence rate of diabetes-related end-stage renal disease (ESRD) has been declining which suggested the condition as secondary to the documented pandemic of type 2 diabetes. A diagram...

  • Alteraciones plaquetarias en la diabetes mellitus tipo 2. Matadamas-Zárate, Cuauhtémoc; Hernández-Jerónimo, Julia; Pérez-Campos, Eduardo; Majluf-Cruz, Abraham // Archivos de Cardiología de México;2009 Supplement 2, Vol. 79 Issue 5, p102 

    Diabetes mellitus is a problem of health worldwide being vascular complications the main causes of morbidity and mortality in this population. Diabetics have a fast atherothrombotic evolution which is worse than that observed for other clinical entities; however, hyperglycemia itself may not...

  • Ischaemia imaging in type 2 diabetic kidney transplant candidates is coronary angiography essential? Sishir Gang; Manish Dabhi; Mohan Manohar Rajapurkar // Nephrology Dialysis Transplantation;Aug2007, Vol. 22 Issue 8, p2334 

    Background. Coronary artery disease (CAD) remains the leading cause of death in type 2 diabetes mellitus (DM) patients undergoing renal transplantation. There is a high prevalence of silent CAD in these patients. Controversy exists regarding the role of dobutamine stress echocardiography (DSE)...

  • Sulfonylurea Treatment of Type 2 Diabetic Patients Does Not Reduce the Vasodilator Response to Ischemia. Spallarossa, Paolo; Rossettin, Pierfranco; Cordone, Stefano; Olivotti, Luca; Brunelli, Claudio; Schiavo, Mara; Cordera, Renzo // Diabetes Care;Apr2001, Vol. 24 Issue 4, p738 

    Presents information on a study which compared the effect of glibenclamide, glimepiride and diet treatment on brachial artery response to acute forearm ischemia among type 2 diabetics. Research design and methods; Results; Conclusions.

  • Phosphodiesterase III Inhibition Increases cAMP Levels and Augments the Infarct Size Limiting Effect of a DPP-4 Inhibitor in Mice with Type-2 Diabetes Mellitus. Birnbaum, Yochai; Castillo, Alexander; Qian, Jinqiao; Ling, Shukuan; Ye, Hongmei; Perez-Polo, Jose; Bajaj, Mandeep; Ye, Yumei // Cardiovascular Drugs & Therapy;Dec2012, Vol. 26 Issue 6, p445 

    Purpose: We assessed whether phosphodiesterase-III inhibition with cilostazol (Cil) augments the infarct size (IS)-limiting effects of MK0626 (MK), a dipeptidyl-peptidase-4 (DPP4) inhibitor, by increasing intracellular cAMP in mice with type-2 diabetes. Methods: Db/Db mice received 3-day MK (0,...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics