Volume 12, Issue 1 (Vol.12 No.1 Apr 2023)                   rbmb.net 2023, 12(1): 42-58 | Back to browse issues page


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Mohamed Mesbah M, Ahmed Rashed L, Ahmed El-Boghdady N, Mohamed Said M. Bone Marrow-Derived Mesenchymal Stem Cells and Pioglitazone or Exendin-4 Synergistically Improve Insulin Resistance via Multiple Modulatory Mechanisms in High-Fat Diet/Streptozotocin-Induced Diabetes in Rats. rbmb.net 2023; 12 (1) :42-58
URL: http://rbmb.net/article-1-1091-en.html
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Abstract:   (1373 Views)
Background: Diabetes mellitus (DM) is a metabolic disease, characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. The current study was designed to assess the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) alone and in combination with pioglitazone (Pz) or exendin-4 (Ex) in high-fat diet/streptozotocin (HFD/STZ)-induced diabetes in rats.

Methods: The rats were subjected to the HFD for three weeks before being injected with a single low dosage of STZ (35 mg/kg bw). The animals were assigned to different treatment groups after type II diabetes mellitus (T2DM) induction was confirmed.

Results: Severe insulin resistance was verified in untreated HFD/STZ T2DM rats, along with the exaggeration of oxidative stress, inflammation, apoptosis, and autophagy suppression in the adipose tissues. Monotherapy of HFD/T2DM rats with BM-MSCs and Pz or Ex alleviated diabetic complications by increasing insulin sensitivity, decreasing apoptosis and inflammation as evidenced by a decrease in serum tumor necrosis factor-alpha, caspase-3, and nuclear factor-kappa B (NF-kB) genes expression and Janus kinase (JNK) protein expression, and enhancing autophagy as revealed by upregulation in beclin and LC3, as well as peroxisome proliferator-activated receptor-g coactivator-1 alpha (PGC-1α) genes expression in the adipose tissues. An augmented ameliorative efficacy was recorded in combined treatments. The biochemical and molecular results were confirmed by histological investigation of pancreatic tissues.

Conclusions: Combining Pz or Ex with BM-MSCs is a synergistic therapeutic option that reduces insulin resistance and subsequent complications in T2DM via multiple molecular mechanisms.
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Type of Article: Original Article | Subject: Biochemistry
Received: 2022/11/10 | Accepted: 2023/01/8 | Published: 2023/08/15

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