Altered glucose metabolism and insulin resistance in cancer-induced cachexia: a sweet poison.

Abstract

Cancer cachexia is a wasting disorder characterised by specific skeletal muscle and adipose tissue loss. Cancer cachexia is also driven by inflammation, altered metabolic changes such as increased energy expenditure, elevated plasma glucose, insulin resistance and excess catabolism. In cachexia, host-tumor interaction causes release of the lactate and inflammatory cytokines. Lactate released by tumor cells takes part in hepatic glucose production with the help of gluconeogenic enzymes. Thus, Cori cycle between organs and cancerous cells contributes to increased glucose production and energy expenditure. A high amount of blood glucose leads to increased production of insulin. Overproduction of insulin causes inactivation of PI3K/Akt/m-TOR pathway and finally results in insulin resistance. Insulin is involved in maintaining the vitality of organs and regulate the metabolism of glucose, protein and lipids. Insulin insensitivity decreases the uptake of glucose in the organs and results in loss of skeletal muscles and adipose tissues. However, looking into the complexity of this metabolic syndrome, it is impossible to rely on a single variable to treat patients having cancer cachexia. Hence, it becomes greater a challenge to produce a clinically effective treatment for this metabolic syndrome. Thus, the present paper aims to provide an understanding of pathogenesis and mechanism underlining the altered glucose metabolism and insulin resistance and its contribution to the progression of skeletal muscle wasting and lipolysis, providing future direction of research to develop new pharmacological treatment in cancer cachexia.