Role of the Kidney in Glucose Homeostasis: The Basis for Pharmacotherapy and Prevention of Cardio-Renal Complications in Diabetes.

Abstract

Energy requirements in the human body are met by fuel mobilization stored in the form of fat, protein and carbohydrate. Fat depots and glycogen storage in muscle and liver represent the largest contributors that sustain essential organic functions and mobility. Protein reserves are intended primarily for structural, biochemical and physiological purposes and are, thus, spared as substrate for oxidation, except under conditions of prolonged starvation. Extracellular free FFA, triglycerides and glucose account for only a minor fraction of the total energy storage, but they are essential sources of energy to organs and tissues in times of need. Therefore, maintenance of appropriate circulating levels of these substrates, particularly glucose, is an important component of fuel homeostasis. In this review, we focus on those mechanisms responsible for maintaining adequate blood glucose concentrations, with an emphasis on the role of the kidney. Renal adaptations to changes in the metabolic milieu, both in healthy and diabetic conditions, will be examined. We will provide a comprehensive description of the pharmacology and therapeutic actions of the sodium-glucose co-transporter 2 inhibitor [SGLT2i] class of drugs, which target the kidney and inhibit the reabsorption of glucose. The renal and cardiovascular benefits of the SGLT2i will be reviewed.