The role of insulin resistance in the development of muscle wasting during cancer cachexia

Abstract

BackgroundCancer cachexia is a complex syndrome associated with multiple metabolic abnormalities. Insulin resistance is present in many cancer patients and may be one mechanism through which muscle wasting occurs.Methods and resultsThe present review examines evidence in support of a role for insulin resistance in the development of muscle wasting during cancer cachexia and identifies areas for future research. Patients suffering from cancer cachexia tend to exhibit insulin resistance and improvements in insulin resistance have the potential to improve cachexia symptoms. In addition, evidence suggests that insulin resistance may occur prior to the onset of cachexia symptoms.ConclusionsFurther investigation of the role of insulin resistance in cancer cachexia is needed. The use of translational research in this area is strongly encouraged, and has important implications for clinical research and the treatment and prevention of cancer cachexia.

Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor disease progression

“…Putative mechanisms implicate tumor-secreted factors, including proinflammatory cytokines (IL6, TNFA), proteolysis by ubiquitin-proteasome and autophagy-related lysosomal pathways, imbalance of catabolism and anabolism, and mitochondrial dysfunction (4,5). Aggressive tumor growth may also interfere with normal cardiac metabolism (6).…”

Challenges in Treatment of Obesity in the Elderly

“…Insulin regulates the amount of skeletal muscle tissue by inducing changes in protein degradation [37]. Under normal conditions ( Figure 2a) the binding of insulin to its receptor activates the phosphatidylinositol 3-kinase (PI3K) protein and the serine threonine kinase (AKT) protein.…”

“…Activation of the AKT protein leads to a decrease in proteolytic activity mediated by the suppression of caspase-3 activity and FoxO (Forkhead box O) protein. In insulin-resistance states (Figure 2b) PI3-kinase and AKT activity is reduced, resulting in an increase of proteolytic activity and a reduction in lean mass [37].…”

Muscle wasting: An overview of recent developments in basic research

“…Overall, the blunting of IGF-1/ IRS-1 signaling not only leads to an inhibition of protein synthesis with concurrent induction of proteolysis, but IRS-1 itself cannot be regenerated after UPS-mediated degradation, thereby leaving the muscle cells unresponsive [29]. Although insulin resistance is noted in many patients with cancer cachexia [50], IGF-1 itself and the IGF-1 receptor are targeted in cancer patients, as they play a role in the growth of several tumors, including pancreatic cancer, which might further impair anabolic signaling in skeletal muscle [51]. However, in non-IGF-1-dependent cancers, IGF-1 supplementation may reduce muscle wasting [52].…”