A phenomenological-based semi-physical model of the kidneys and its role in glucose metabolism

The kidneys play an important role in glucose homeostasis in three ways: Via endogenous glucose production from non-carbohydrate precursors (e.g. glutamine, lactate, alanine, glycerol) during both post-prandial and post-absorptive states; via glucose filtration and reabsorption by the glomerulus and proximal tubule, respectively; and via glucose utilization and the elimination of its excess in the urine when glucose levels exceed 180 mg/dl. The renal release of glucose into the circulation occurs mainly in the renal cortex and results from the glucose phosphorylating capacity of those renal cells, meaning that, cells in the renal cortex can form glucose-6-phosphate. Considering glucose filtration and reabsorption, the kidneys filtrate and reabsorb all circulating glucose, rendering the urine virtually glucose-free in a healthy person. Finally, the kidneys take up glucose from the circulation for energetic self-supply. Besides their role in glucose metabolism, the kidneys are the major site of insulin clearance from the systemic circulation, removing approximately 50% of peripheral insulin. In this regard, insulin clearance by kidneys occurs by degradation in the proximal tubule after being filtered in the glomerulus. All the aforementioned mechanisms affect the glucose concentration levels in the blood, preventing the parametrization of a mathematical model for patients with diabetes mellitus, in the implementation of an artificial pancreas. Aiming for a complete physiological model of the glucose homeostasis, a physiological submodel of the kidneys is presented in a way not described in the literature so far. This submodel is a phenomenological-based semi-physical model with a basic structure rooted in the conservation law and for which the parameters are interpretable. The model's results coincide well with the available clinical data reported for kidney functions associated with glucose and insulin. (C) 2020 Elsevier Ltd. All rights reserved.