Burn injury insulin resistance and central nervous system complications: A review

Abstract

Insulin resistance is a major underlying and preexisting event in chronic metabolic disorders. However, this is also an acute, de novo condition in critical burn survivors and other emergency episodes. Irrespective to its proximal trigger in burn pathology, peripheral insulin resistance results from an impaired receptor’s signaling to accurately transduce the hormonal message, leading to hyperglycemia, hypermetabolism and catabolia. Elevation of stress hormones, pro-inflammatory cytokines, along with spillover of mitochondria-derived free radicals lead to an insulin receptor impairment that counteracts insulin anabolic actions. These post-burn metabolic-inflammatory disorders could last for years and embraces the central nervous system. The persistence of these events may suggest the existence of a metabolic memory beyond that described for diabetes, in which the involvement of epigenetic mechanisms remains to be investigated. The brain is a target organ of multiple post-burn complications which seem to be set forth through peripheral/central inflammation, nitric oxide imbalance, oxidative stress, and ultimately neuronal insulin resistance and insufficient glucose utilization. From neuroses to dementia post-burn neurological complications are described as clinical expression of neuronal degeneration, apoptosis, and synapsis rupture. All these events may represent the collapse of the neuroprotective actions due to the failed insulin axis. Although peripheral and central insulin resistance may be mechanistically determined by different players, for both scenarios, mitochondria appear to be central in the energy homeostasis failure. This review includes the most recently identified pathogenic drivers on peripheral and central insulin resistance, whereas it also reveals critical breaches that may translate in future therapeutic interventions. Keywords: Hyperglycemia, Burn injury, Insulin, Insulin resistance, Insulin receptor, Post-burn cognitive impairment