Cancer-drug induced insulin resistance: Innocent bystander or unusual suspect

BGP-15 Protects against Oxaliplatin-Induced Skeletal Myopathy and Mitochondrial Reactive Oxygen Species Production in Mice

“…Chemotherapeutic agents target the molecular characteristics of cancerous cells, such as rapid replication, to chemically-induce cell death (de Gramont et al, 2000; Sorensen et al, 2016). However, due to its non-specific and systemic mode of action, chemotherapy also elicits effects on healthy tissues causing the classic side-effects attributable to anti-cancer therapy including nausea, vomiting, cardio-toxicity, immune disorders, peripheral and axial neuropathy, hair and weight loss and debilitative fatigue (Greene et al, 1993; Zitvogel et al, 2008; Gilliam and St Clair, 2011; National Cancer Institute, 2012; Ariaans et al, 2015). These side-effects often limit treatment tolerability, efficacy and therapeutic options, sometimes leading to the cessation of treatment all together and ultimately reducing patient quality of life and prognosis due to the development of co-morbidities (Gilliam and St Clair, 2011; Scheede-Bergdahl and Jagoe, 2013; Argilés et al, 2015; Cheregi et al, 2015).…”

“…These side-effects often limit treatment tolerability, efficacy and therapeutic options, sometimes leading to the cessation of treatment all together and ultimately reducing patient quality of life and prognosis due to the development of co-morbidities (Gilliam and St Clair, 2011; Scheede-Bergdahl and Jagoe, 2013; Argilés et al, 2015; Cheregi et al, 2015). Emerging evidence suggests that the skeletal muscle is also a target of chemotherapy-induced atrophy (Pfeiffer et al, 1997), weakness and fatigue (Gilliam and St Clair, 2011), dysfunction (Scheede-Bergdahl and Jagoe, 2013; Bredahl et al, 2016) and insulin resistance (Ariaans et al, 2015). These effects appear to be more pronounced when chemotherapy is administered in childhood, due to the hyperplastic and hypertrophic nature of skeletal muscle at this early stage of life and persist well into adulthood (Ness et al, 2007; Scheede-Bergdahl and Jagoe, 2013; Ariaans et al, 2015).…”

“…Emerging evidence suggests that the skeletal muscle is also a target of chemotherapy-induced atrophy (Pfeiffer et al, 1997), weakness and fatigue (Gilliam and St Clair, 2011), dysfunction (Scheede-Bergdahl and Jagoe, 2013; Bredahl et al, 2016) and insulin resistance (Ariaans et al, 2015). These effects appear to be more pronounced when chemotherapy is administered in childhood, due to the hyperplastic and hypertrophic nature of skeletal muscle at this early stage of life and persist well into adulthood (Ness et al, 2007; Scheede-Bergdahl and Jagoe, 2013; Ariaans et al, 2015). Since skeletal muscle has a high energy requirement, and thus a high mitochondrial density, emerging data suggests that skeletal muscle pathology may be underpinned by damage induced to the mitochondrial by chemotherapy administration (Davies and Doroshow, 1986; Doroshow and Davies, 1986; Sarosiek et al, 2013; Tabassum et al, 2015).…”

Moieties in antidiabetic drugs as a target of insulin receptors in association with common neurological disorders

“…In AD, this imbalance may affect cortisol, noradrenaline, stress components and reactive oxygen species (ROS), the result of which is membrane damage and an insulin-resistant brain state leading to a decrease in glucose/energy metabolism (10). Presently, it has been discovered that treatments with cancer therapeutic agents such as glucocorticoids, chemotherapy, hormonal therapies and targeted drugs can induce insulin resistance (11).…”

“…Certain investigators suggest that the capacity of leptin in promoting stress-induced dopaminergic function is crucial in the production of pathological states including mood, disorders in the use of drugs and eating promoting obesity, where dopamine has an important role (12). The study by Ariaans et al (11) indicates that diabetes is associated with reduced basal dopamine levels in the nucleus accumbens. Possibly, the free radicals in the CNS are responsible for the induction of these disorders (13).…”