Insulin resistance and epilepsy: an emerging pathophysiological nexus.

Epilepsy is a neurological disorder that is chronic, and the condition is characterized by the occurrence of seizures generally attributed to anomalous neuronal excitability along with malfunction in the networks. New evidence suggests that metabolic unsteadiness, primarily insulin insensitivity, can add to the pathophysiology of epilepsy. Insulin, which used to be regarded as having primary control over the peripheral glucose metabolism process, is today recognized to be a crucial neuromodulator in the brain, and it influences the process of synaptic plasticity, neurotransmitter activity, and neuronal survival. Interference with central insulin signalling has been linked to many neurodegenerative and neuropsychiatric diseases, and, recently, there has also been evidence that it is important in the pathogenesis of epilepsy. This review explores the interdependent nature of insulin resistance and epilepsy and examines how metabolic dysfunction can cause a reduction in seizure threshold through a pathway of oxidative stress, neuroinflammation, and mitochondrial dysfunction. Furthermore, it underscores the significance of epilepsy and its treatment approaches, specifically the use of one or more anti-seizure drugs, which can exacerbate insulin resistance and perpetuate a vicious cycle. The neuroendocrine coordination between glucose homeostasis and insulin signalling and neuronal excitability opens up new insights into shared molecular pathways, such as the mTOR, TNF-alpha, and GLUT4 pathways. Therapeutic implications discussed in the research also mention the potential role of insulin-sensitizing medication (e.g., metformin), lifestyle changes, and ketogenic dietary measures in supporting seizure control and the improvement of metabolic outcome. The review focuses on the need to regard insulin resistance as a therapeutic target as well as comorbidity in epilepsy care through the combination of neurological and metabolic perspectives.