Reciprocal relationship between neurodegeneration-related miRNAs and neurohormones in diabetes mellitus patients: The possible mechanism of high glucose neurotoxicity

Toqa Alabyadh, Leila Sadeghi, Mohammad Ali Hosseinpour Feizi

Abstract


Background: Diabetes mellitus (DM) is a metabolic syndrome that causes blood glucose to remain consistently above normal. High glucose concentrations in the neuronal niche can harm neurons permanently. Some DM-related molecular events are found to cause neurological abnormalities and cognitive dysfunctions. Dopamine and oxytocin are important neurohormones that are regulated by miRNAs and could also reorganize neural function-related miRNA networks. Therefore, the purpose of this study was to assess how neurohormones and miRNAs linked to neurodegeneration interact in DM patients.

Methods: For this purpose, blood samples related to type 1 (T1DM) and type 2 (T2DM) of diabetes and non-diabetic controls were used to measure hormones (dopamine, oxytocin, and thyroid hormones) by using a specific ELISA kit and circulating miRNAs by RT-PCR method.

Results: Data revealed a significant reduction of dopamine and oxytocin in both types of DM, which are accompanied by miR-27a, miR-107, and miR-191 up-regulation. PTEN-induced putative kinase 1 (PINK1) protein expression is primarily inhibited by miR-27a, which leads to dopaminergic cell death and consequently reduces dopamine synthesis and release. We also found a significant decrease in miR-23a and miR-128 levels in DM that may promote dopaminergic cell vulnerability, possibly through attenuation of mitochondrial complex I. Comparing the data related to both types of DM confirmed that miR191 and miR-128 levels in T2DM are higher than in T1DM.

Conclusion: It was discovered that miRNAs and neurohormones have a reciprocal interaction that may make them a promising treatment target for DM.

Keywords: Diabetes mellitus, Neurodegeneration, miRNAs, Dopamine, Oxytocin, Diabetes related neurotoxicity


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References


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DOI: http://dx.doi.org/10.62940/als.v12i3.2354

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