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Vitamin B3; Cytoskeletal proteins; Neuroprotection

Introduction

Hyperglycemia, a defining feature of diabetes mellitus (DM), one of the most serious heterogeneous groups of disorders with a clear genetic component, can result in a variety of complications, including neuropathy in both types of DM. Type 2 DM (T2D) is more often linked to insulin resistance than type 1 DM (T1D), which is primarily an autoimmune disease brought on by the death of the islet beta-cells that produce insulin. The most common DM impairment, diabetic neuropathy (DN), is a group of complex syndromes that disrupt the structure and function of the brain and peripheral nerves, affecting the nervous system as a whole. DN can also increase the risk of developing microstructural alterations and cognitive dysfunctions [1-3].

Methodology

While peripheral diabetic neuropathy (DN) is the most prevalent DM complication that results in mortality and morbidity, diabetes also affects the central nervous system (CNS). Since there is no proven treatment for brain dysfunctions, it is necessary to fully understand the underlying pathogenetic mechanisms in order to create novel, efficient approaches to their management. Vitamin B3 (nicotinic acid and nicotinamide, NAm) may have different but equally significant roles in the treatment of brain dysfunctions, according to theory. Since NAm shields islet cells from cytotoxic effects, a substantial body of research has been conducted on the drug as a proven effective preventive and treatment agent for a variety of complications associated with insulindependent diabetes mellitus. Nicotinic acid, which shares structural similarities with NAm, is known to increase insulin secretion and may be beneficial for addressing insulin resistance and related issues in type 2 diabetes [4,5].

However, gamma-aminobutyric acid (GABA) has been shown to be a safe agent that facilitates the transformation of alpha cells back into functional beta-like cells, which in turn increases the production of insulin. N-nicotinoyl-GABA (N-GABA), also referred to as pikamilone, is a synthetic combination of nicotinic acid and GABA that was first created as a nootropic and anxiolytic medication to improve cognitive function and stave off dementia. Through a particular ligand-mediated mechanism, we had previously shown that NAm, and particularly N-GABA, can have positive effects on the brain GABA-benzodiazepine complex that is impaired by DM [6-8].

The hyperglycemic state can cause dysregulation of several extracellular and intracellular signaling cascades, which can lead to CNS dysfunctions and functional, metabolic, and structural changes in brain neuronal functions. Furthermore, our team has previously shown that PARP activation plays a role in the etiology of Type 1 diabetes-related kidney hypertrophy, proliferative retinopathy, and diabetic peripheral neuropathy. We have also shown that PARP inhibitors are useful in the prevention and management of these complications [9,10].

Conclusion

Among the many factors that lead to CNS dysfunctions caused by hyperglycemia developed by increased mitochondrially produced superoxide, vascular impairments, changes in cell immunity, etc., oxidative stress is one of the most important ones . Despite the close relationship between neural and vascular components, changes in blood vessel structure and function may result in cerebrovascular dysfunction in people with type 1 diabetes. It has recently been suggested that VEGF, or vascular endothelial growth factor, regulates adult neurogenesis, neuroprotection, brain endothelial function, and neural development. While DM-induced disruptions of VEGF signaling in the heart, kidney, eye, and limb vasculature have been documented, the brain has received less research attention.

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