Abstract
Insulin represents the paramount anabolic hormone and the master regulator of glucose, lipid, and protein metabolism. This chapter describes the sequential stages of the physiologic journey of insulin in the human body, from its synthesis/secretion to its action in peripheral tissues and, ultimately, to its clearance and degradation. These stages include i) insulin synthesis and release from pancreatic beta cells; ii) insulin first-pass metabolism and partial clearance in the liver; iii) insulin action on the vasculature and exit from the capillary beds; iv) insulin action in peripheral and central target tissues (skeletal muscle, adipose tissue, liver, and central nervous system); and v) final insulin degradation in the kidney. Each of these stages is regulated by complex intracellular mechanisms that take place in different tissues and allow for the anabolic actions of insulin. Understanding the abovementioned stages is pivotal to comprehending the clinical consequences of impaired insulin secretion and action, as defects in one or more of these stages can be associated with the development of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. Additionally, a thorough knowledge of the insulin bodily journey can assist clinicians in therapeutic decision-making for diabetic patients on exogenous insulin therapy in different clinical settings.