Mechanism (biology)

Subversion

Cell biology

Type 2 diabetes

Philosophy

Biology

Endocrinology

Metabolism

Cancer research

Biochemistry

Insulin

Leukemia

Secretion

Incretin

Immunology

Genetics

Homeostasis

Politics

Political science

Insulin resistance

Epistemology

Chemistry

Cancer

Glucose homeostasis

Cellular metabolism

Carbohydrate metabolism

Diabetes mellitus

Cancer Cell

Highlights•Leukemia subverts systemic glucose metabolism by induction of insulin resistance (IR)•Aberrancies in adipose tissue, pancreas, gut, and microbiota contribute to IR•Leukemic progression is attenuated by modulations of systemic glucose metabolism•Leukemia patients display characteristics of IRSummaryFrom an organismal perspective, cancer cell populations can be considered analogous to parasites that compete with the host for essential systemic resources such as glucose. Here, we employed leukemia models and human leukemia samples to document a form of adaptive homeostasis, where malignant cells alter systemic physiology through impairment of both host insulin sensitivity and insulin secretion to provide tumors with increased glucose. Mechanistically, tumor cells induce high-level production of IGFBP1 from adipose tissue to mediate insulin sensitivity. Further, leukemia-induced gut dysbiosis, serotonin loss, and incretin inactivation combine to suppress insulin secretion. Importantly, attenuated disease progression and prolonged survival are achieved through disruption of the leukemia-induced adaptive homeostasis. Our studies provide a paradigm for systemic management of leukemic disease.Graphical abstract

Subversion of Systemic Glucose Metabolism as a Mechanism to Support the Growth of Leukemia Cells