title: Effect of impaired glucose tolerance on cardiac dysfunction in a rat model of prediabetes.
abstract: BACKGROUND
  The effect of impaired glucose tolerance (IGT) on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.
  
  
  METHODS
  The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography. Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor (MIF) and G-protein coupled receptor kinase 2 (GRK2) were detected by Western blotting in cardiac tissue lysates.
  
  
  RESULTS
  Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls, increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively (F = 15.370, P = 0.003). Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction (EF) being (68.59 ± 6.62)% in IGT rats vs. (81.07 ± 4.59)% in controls (t = 4.020, P = 0.002). There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.
  
  
  CONCLUSIONS
  IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.
authors.affiliation: Medical Research Center, Guangdong General Hospital, Guangdong Provincial Cardiovascular Institute, Guangdong Institute of Clinical Pharmacology, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
authors.forename: Jia-Liang
authors.initials: JL
authors.lastname: Liang
authors.forename: Zhi-Kuan
authors.initials: ZK
authors.lastname: Feng
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Liu
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.forename: Yong-Heng
authors.initials: YH
authors.lastname: Fu
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Shan
authors.forename: Jie-Ning
authors.initials: JN
authors.lastname: Zhu
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Lin
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D004452:Echocardiography; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D018149:Glucose Intolerance / Q000139:chemically induced / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D020287:In Situ Nick-End Labeling; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D051381:Rats; D013311:Streptozocin / Q000633:toxicity
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D013311:Streptozocin; C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat