Koncsos 2016 Am J Physiol Heart Circ Physiol

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Koncsos G, Varga ZV, Baranyai T, Boengler K, Rohrbach S, Li L, Schlüter KD, Schreckenberg R, Radovits T, Oláh A, Mátyás C, Lux Á, Al-Khrasani M, Komlódi T, Bukosza N, Máthé D, Deres L, Barteková M, Rajtík T, Adameová A, Szigeti K, Hamar P, Helyes Z, Tretter L, Pacher P, Merkely B, Giricz Z, Schulz R, Ferdinandy P (2016) Diastolic dysfunction in prediabetic male rats: role of mitochondrial oxidative stress. Am J Physiol Heart Circ Physiol 311:H927-43.

» PMID: 27521417 Open Access

Koncsos Gabor, Varga Zoltan V, Baranyai Tamas, Boengler Kerstin, Rohrbach Susanne, Li Ling, Schlueter Klaus-Dieter D, Schreckenberg Rolf, Radovits Tamas, Olah Attila, Matyas Csaba, Lux Arpad, Al-Khrasani Mahmoud, Komlodi Timea, Bukosza Nora, Mathe Domokos, Deres Laszlo, Bartekova Monika, Rajtik Tomas, Adameova Adriana, Szigeti Krisztian, Hamar Peter, Helyes Zsuzsanna, Tretter Laszlo, Pacher Pal, Merkely Bela, Giricz Zoltan, Schulz Rainer, Ferdinandy Peter (2016) Am J Physiol Heart Circ Physiol

Abstract: Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect of prediabetes on cardiac function and to characterize parameters and pathways associated with deteriorated cardiac performance. Long-Evans rats were fed with either control or high-fat chow for 21 wk and treated with a single low dose (20 mg/kg) of streptozotocin at week 4 High-fat and streptozotocin treatment induced prediabetes as characterized by slightly elevated fasting blood glucose, impaired glucose and insulin tolerance, increased visceral adipose tissue and plasma leptin levels, as well as sensory neuropathy. In prediabetic animals, a mild diastolic dysfunction was observed, the number of myocardial lipid droplets increased, and left ventricular mass and wall thickness were elevated; however, no molecular sign of fibrosis or cardiac hypertrophy was shown. In prediabetes, production of reactive oxygen species was elevated in subsarcolemmal mitochondria. Expression of mitofusin-2 was increased, while the phosphorylation of phospholamban and expression of Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3, a marker of mitophagy) decreased. However, expression of other markers of cardiac auto- and mitophagy, mitochondrial dynamics, inflammation, heat shock proteins, Ca2+/calmodulin-dependent protein kinase II, mammalian target of rapamycin, or apoptotic pathways were unchanged in prediabetes. This is the first comprehensive analysis of cardiac effects of prediabetes indicating that mild diastolic dysfunction and cardiac hypertrophy are multifactorial phenomena that are associated with early changes in mitophagy, cardiac lipid accumulation, and elevated oxidative stress and that prediabetes-induced oxidative stress originates from the subsarcolemmal mitochondria.

Keywords: Diabetic cardiomyopathy, High-fat diet, Obesity, Reactive oxygen species, Type 2 diabetes Bioblast editor: Kandolf G, Komlodi T O2k-Network Lab: DE Giessen Rohrbach S, HU Budapest Tretter L


Labels: MiParea: Respiration  Pathology: Cardiovascular, Diabetes  Stress:Oxidative stress;RONS  Organism: Rat  Tissue;cell: Heart  Preparation: Isolated mitochondria 


Coupling state: OXPHOS  Pathway: N, S, NS  HRR: Oxygraph-2k 

Labels, 2018-04