ArticleHeliyon2022
Regulation of the apoptosis/autophagy switch by propionic acid in ventromedial hypothalamus of rats with type 2 diabetes mellitus.
Article in Heliyon, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Combined Administration of Metformin and Propionate Reduces the Degree of Oxidative/Nitrosative Damage of Hypothalamic Neurons in Rat Model of Type 2 Diabetes Mellitus.Molecular neurobiology · 2025Article
- Knockdown of PDPN in astrocytes reduces hippocampal inflammation in T2DM mice.Frontiers in immunology · 2025Article
- Could the Propionic Acid Treatment in Combination with Metformin be Safe for the Small Intestine of Diabetic Rats?Endocrine, metabolic & immune disorders drug targets · 2024Article
- Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models.Journal of nanobiotechnology · 2023Article
- Microfluidic Distillation System for Separation of Propionic Acid in Foods.Micromachines · 2023Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Hypothalamic dysregulation may cause abnormal glucose metabolism and type 2 diabetes mellitus (T2DM). The balance between autophagy and apoptosis is important for maintaining cellular/tissue homeostasis and may be disrupted in T2DM. Objectives: Since propionic acid (PA) exerts neuroprotective effects, the aim was to investigate its effects on apoptosis/autophagy switch in the ventromedial hypothalamus (VMH) of T2DM rats. Materials and methods: Male Wistar rats were divided: 1) control; 2) T2DM; groups that received (14 days, orally): 3) metformin (60 mg/kg); 4) sodium salt of PA (60 mg/kg); 5) PA + metformin. Western blotting (Bax, Bcl-xl, LC3, Beclin-1, caspase-3), RT-PCR (Bax, Bcl-xl, LC3, Beclin-1), transmission electron microscopy and immunohistochemical staining (Bax, Bcl-xl) were performed on the VMH samples. Results: T2DM-induced apoptosis and mitoptosis, enlarged endoplasmic reticulum (ER) tubules/cisterns were observed in VMH, and accompanied by an imbalance of pro- and anti-apoptotic factors: elevation of pro-apoptotic markers Bax and caspase-3, decrease in autophagy protein LC3 and anti-apoptotic Bcl-xl. Metformin and PA administration partially improved VMH ultrastructural changes by reducing mitochondrial swelling and diminishing the number of apoptotic neurons. Metformin inhibited neuronal apoptosis, however, caused reactive astrogliosis and accumulation of lipofuscin granules. Elevated number of autophagosomes was associated with the LC3, Beclin-1 and Bcl-xl increase and decrease in Bax and caspase-3 vs. T2DM. PA switched cell fate from apoptosis to autophagy by elevating LC3 and Beclin-1 levels, increasing Bcl-xl content that altogether may represent adaptive response to T2DM-induced apoptosis. PA + metformin administration lowered relative area of ER membranes/cisterns vs. control, T2DM and metformin, and was optimal considering ratio between the pro-apoptotic, anti-apoptotic and autophagy markers. Conclusion: T2DM was associated with apoptosis activation leading to impairments in VMH. PA in combination with metformin may be effective against diabetes-induced cell death by switching apoptosis to autophagy in VMH.
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