Bone Marrow-Derived Mesenchymal Stem Cells and Pioglitazone or Exendin-۴ Synergistically Improve Insulin Resistance via Multiple Modulatory Mechanisms in High-Fat Diet/Streptozotocin-Induced Diabetes in Rats
سال انتشار: 1402
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 61
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شناسه ملی سند علمی:
JR_RBMB-12-1_005
تاریخ نمایه سازی: 31 مرداد 1402
چکیده مقاله:
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-۴ (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 (۳۵ mg/kg bw). The animals were assigned to different treatment groups after type II diabetes mellitus (T۲DM) induction was confirmed.
Results: Severe insulin resistance was verified in untreated HFD/STZ T۲DM rats, along with the exaggeration of oxidative stress, inflammation, apoptosis, and autophagy suppression in the adipose tissues. Monotherapy of HFD/T۲DM 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-۳, 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 LC۳, as well as peroxisome proliferator-activated receptor-g coactivator-۱ alpha (PGC-۱α) 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 T۲DM via multiple molecular mechanisms.
کلیدواژه ها:
Exendin-۴ ، High-fat diet ، Mesenchymal stem cells ، Pioglitazone ، Streptozotocin ، Type II diabetes mellitus.
نویسندگان
Mohamed Mohamed Mesbah
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Laila Ahmed Rashed
Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
Noha Ahmed El-Boghdady
Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Mahmoud Mohamed Said
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
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