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Khadeeja Naeem Zwayyer
Leila Sadeghi
Gholamreza Dehghan


Neurological abnormalities, miR-16, Insulin resistance, Type 2 diabetes, miRNAs network, Non-enzymatic glycation


Aim: Type 2 diabetes mellites (T2DM) is a chronic metabolic disorder associated with oxidative stress, increased inflammation, altered energy metabolism and neurological abnormalities. Therefore, this study aimed to clarify some neurological ambiguities in diabetes.  By considering master regulatory role of miRNAs in biological process, we evaluated some neuroactive miRNAs (miR-125a, Let-7 miRNA, miR-181c, miR-504, miR-16) and neurohormones such as Gamma-aminobutyric acid (GABA), serotonin and dopamine in T2DM patients.

Methods: This study were performed on 30 T2DM patients and 30 non-diabetic controls. The level of GABA, serotonin, dopamine and biochemical parameters were determined by specific ELISA kit in blood serum samples. Also, the relative contents of the miRNAs were evaluated by the real-time quantitative polymerase chain reaction (RT-qPCR) analysis.

Results: The obtained results show that dopamine and serotonin increased in hyperglycemia condition possibly due to upregulation of miR-181c and miR-125a and down-regulation of miR-16. The mentioned changes in miRNAs network also could be considered as a cause of insulin resistance (IR). Reduced content of miR-16 could lead to reduced glucose uptake that was observed in diabetes. Circular concentration of GABA decreased also that could be considered as a reason for IR and decreased glucose uptake. GABA is an excitatory neurotransmitter and its reduction could be a possible cause for dementia related disease.

Conclusion: This study revealed the examined miRNAs plays essential role in oxidative stress, inflammation and IR in T2DM and have therapeutic potential. Based on neuroendocrine abnormalities in diabetes, exogenous hormones could be considered as therapeutic agents to control the metabolism rate and decrease the neurological side effects in T2DM.  

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