Insulin and the Physiology of Carbohydrate Metabolism

Abstract

The discovery of insulin nearly a century ago revolutionized the treatment of diabetes mellitus, particularly type 1 diabetes mellitus (T1DM), and initiated extensive research into the effects of insulin. At approximately the same time, it was shown that patients with cancer were characterized by glucose intolerance and impaired insulin sensitivity of glucose metabolism has been subsequently found in cancer [1, 2]. Insulin, a peptide hormone produced by the β cells in the pancreas, is anabolic, as it stimulates synthesis of glycogen, protein, and triglycerides and it suppresses glucose production by the body, while stimulating glucose uptake from the circulation [3]. Moreover, insulin action is tissue-specific, since it depends on the binding of insulin to its cell-surface receptor. The insulin receptor, which is composed of two transmembrane β chains and two extracellular α chains, has intrinsic tyrosine kinase activity [4, 5] and binding of insulin to its receptor initiates a signaling cascade characterized by phosphorylation events and genomic effects. The insulin receptor is expressed in various tissues, including the most widely studied insulin sensitive tissues, namely liver, skeletal muscle, adipose tissue, and selective regions of the brain. Insulin has mitogenic effects [6], but the ensuing discussion will highlight the metabolic actions of insulin. Furthermore, although insulin regulates the metabolism of all three macronutrients [7], which is interlinked, the focus will be on insulin’s effect on carbohydrate metabolism.