骨髓来源的间充质干细胞和吡格列酮或外泌肽-4在高脂饮食/链脲佐菌素诱导的大鼠糖尿病中通过多种调节机制协同改善胰岛素抵抗。

IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mohamed Mesbah Mohamed, Laila Ahmed Rashed, Noha Ahmed El-Boghdady, Mahmoud Mohamed Said
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引用次数: 0

摘要

背景:糖尿病是一种代谢性疾病,其特征是胰岛素分泌和/或胰岛素作用缺陷导致的高血糖。本研究旨在评估骨髓间充质干细胞(BM-MSCs)单独和与吡格列酮(Pz)或艾塞那丁-4(Ex)联合治疗高脂饮食/链脲佐菌素(HFD/STZ)诱导的大鼠糖尿病的潜力。方法:大鼠在注射单一低剂量STZ(35 mg/kg bw)之前接受HFD三周。在确认II型糖尿病(T2DM)诱导后,将动物分配到不同的治疗组。结果:在未经治疗的HFD/STZ T2DM大鼠中证实了严重的胰岛素抵抗,同时脂肪组织中的氧化应激、炎症、细胞凋亡和自噬抑制加剧。BM-MSCs和Pz或Ex对HFD/T2DM大鼠的单一治疗通过增加胰岛素敏感性、减少细胞凋亡和炎症来减轻糖尿病并发症,如血清肿瘤坏死因子α、胱天蛋白酶-3和核因子κB(NF-κB)基因表达和Janus激酶(JNK)蛋白表达的降低所证明的,以及通过上调脂肪组织中的beclin和LC3以及过氧化物酶体增殖物激活的受体-γ共激活因子-1α(PGC-1α)基因表达来增强自噬。在联合治疗中记录了增强的改善效果。胰腺组织的组织学研究证实了生化和分子结果。结论:将Pz或Ex与骨髓间充质干细胞结合是一种协同治疗选择,可通过多种分子机制降低T2DM的胰岛素抵抗和随后的并发症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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-κB) 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-γ 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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来源期刊
Reports of Biochemistry and Molecular Biology
Reports of Biochemistry and Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
2.80
自引率
23.50%
发文量
60
审稿时长
10 weeks
期刊介绍: The Reports of Biochemistry & Molecular Biology (RBMB) is the official journal of the Varastegan Institute for Medical Sciences and is dedicated to furthering international exchange of medical and biomedical science experience and opinion and a platform for worldwide dissemination. The RBMB is a medical journal that gives special emphasis to biochemical research and molecular biology studies. The Journal invites original and review articles, short communications, reports on experiments and clinical cases, and case reports containing new insights into any aspect of biochemistry and molecular biology that are not published or being considered for publication elsewhere. Publications are accepted in the form of reports of original research, brief communications, case reports, structured reviews, editorials, commentaries, views and perspectives, letters to authors, book reviews, resources, news, and event agenda.
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