Exp Clin Endocrinol Diabetes 2018; 126(01): 27-38
DOI: 10.1055/s-0043-106859
Article
© Georg Thieme Verlag KG Stuttgart · New York

Mitochondrial Dysfunction in Diabetic Cardiomyopathy: Effect of Mesenchymal Stem Cell with PPAR-γ Agonist or Exendin-4

Mohamed Abd Elaziz Wassef
1   Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Cairo University
,
Ola M. Tork
2   Medical Physiology Department, Faculty of Medicine, Cairo University
,
Laila A. Rashed
1   Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Cairo University
,
Walaa Ibrahim
1   Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Cairo University
,
Heba Morsi
1   Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Cairo University
,
Dina Mohamed Mekawy Rabie
1   Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Cairo University
› Author Affiliations
Further Information

Publication History

received 10 November 2016
revised 14 March 2017

accepted 22 March 2017

Publication Date:
27 April 2017 (online)

Abstract

Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4. All treatments were started after 6 weeks from induction of diabetes and continued for the next 4 weeks. Blood samples were collected for assessment of glucose, insulin, and cardiac enzymes. Hearts were removed and used for isolated heart studies, and gene expression of: myocyte enhancer factor-2 (Mef2), peroxisome proliferator-activated receptor gamma coactivator1-alpha (PGC1α), nuclear factor kappa B (NFKB) and autophagic markers: light chain 3 (LC3) and beclin by real-time reverse transcription-polymerase chain reaction. The cardiac mitochondrial protein levels of cardiolipin and uncoupler protein 2 (UCP2) were assessed by ELISA and western blot technique, respectively. Treated groups showed significant improvement in left ventricular function associated with improvement in the cardiac injury and myopathic markers compared to the non treated diabetic group. NFKB was down-regulated while cardiolipin, PGC1α, LC.3 and beclin were up-regulated in all treated groups. These data suggest that the cardioprotective effects of MSCs, exendin-4 or pioglitazone based on their ability to improve mitochondrial functions through targeting inflammatory and autophagy signaling. The co- administration of pioglitazone or exendin-4 with MSCs showed significant superior improvement compared with MSCs alone, indicating the ability to use them in supporting cardioprotective effects of MSCs.