title: Methylglyoxal chronic administration promotes diabetes-like cardiac ischaemia disease in Wistar normal rats.
abstract: OBJECTIVE
  The influence of lifestyle is well documented, especially the diet regime, in the development of type 2 diabetes (T2D) and associated cardiovascular diseases. Diabetic patients have increased risk of suffering cardiac ischemia and impaired response to such accidents. Methylglyoxal (MG) circulates at high concentration in diabetics' blood and is linked to the development of diabetes chronic complications. We propose that besides promoting the cardiovascular disease, MG may also negatively regulate the endogenous cardioprotection pathways after ischemia.
  
  
  RESULTS
  We performed a comparative study between three animal groups: normal Wistar (W), type 2 diabetic non-obese Goto-Kakizaki (GK) and normal rats submitted to MG chronic administration (3 months) with gradually enhanced concentration, up to 75 mg/Kg (WMG). Hearts were submitted to different experimental conditions: control, ischemia and ischemia-reperfusion. Levels of oxidative stress markers, advanced glycation end-products (AGEs) and their receptors (RAGEs) were evaluated. The serine/threonine protein kinase Akt (Akt), crucial for cardiomyocytes recovery after ischemia, and apoptosis markers were also assessed. Levels of MG, systemic and cardiac oxidative stress markers, AGEs and RAGEs were similar in GK and WMG groups. Akt protein was negatively regulated by MG, leading to impaired apoptotic markers.
  
  
  CONCLUSIONS
  Chronic MG administration to normal rodents mimicked most diabetic alterations, being associated with the development of cardiovascular disease and the impairment of survival pathways. Our results demonstrate the negative effect of MG rich diet in healthy animals and suggest the potential of methylglyoxal as a therapeutic target in diabetes.
authors: Laboratory of Physiology, Institute of Biomedical Research in Light and Image (IBILI), Faculty of Medicine of University of Coimbra (FMUC), Coimbra, Portugal. Electronic address: joanacrisostomo@hotmail.com.
authors: J
authors: J
authors: Crisóstomo
authors: P
authors: P
authors: Matafome
authors: D
authors: D
authors: Santos-Silva
authors: L
authors: L
authors: Rodrigues
authors: C M
authors: CM
authors: Sena
authors: P
authors: P
authors: Pereira
authors: R
authors: R
authors: Seiça
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced*; D018384:Oxidative Stress / Q000187:drug effects; D011765:Pyruvaldehyde / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde
keywords: Cardiac ischemia; Hyperglycemia; Methylglyoxal; Type 2 diabetes