Renal Function and Glucose Homeostasis PDF

Taken from https://www.newcastle-hospitals.nhs.uk/services/endocrine-and-thyroid-surgery/ BS31019 – Renal function and its role in glucose homeostasis Dr Claire Y Hepburn Learning outcomes Demonstrate the function of the renal system in homeostasis Demonstrate the r...

Taken from https://www.newcastle-hospitals.nhs.uk/services/endocrine-and-thyroid-surgery/ BS31019 – Renal function and its role in glucose homeostasis Dr Claire Y Hepburn Learning outcomes Demonstrate the function of the renal system in homeostasis Demonstrate the role of the kidneys in glucose handling Describe how renal glucose reabsorption is quantified Recommended reading Medical Physiology – Chapter 5 – Transport of Solutes and Water Medical Physiology – Chapter 36 – Transport of Urea, Glucose, Phosphate, Calcium, Magnesium, and Organic Solutes BS31013 – Lecture 1 - Membrane transport Osmosis – Tubular Reabsorption of Glucose https://youtu.be/MePBpMhVUQ4?feature=shared The renal system The renal system consists of paired kidneys, paired ureters, a bladder and a urethra Primarily concerned with filtration, secretion and reabsorption Maintaining water balance. Maintaining proper osmolarity of body fluids. Regulating the quantity and concentration of most extracellular fluid (ECF) ions Maintaining plasma volume. Maintaining acid-base balance. Excreting end products of bodily metabolism. Excreting foreign compounds. Producing erythropoietin Producing renin. Converting vitamin D into its active form. Glucose homeostasis. The kidneys filter our entire plasma volume (~3 L) 60 times each day  The renal system Adapted from Gray’s Anatomy for Students, 5e, 2024 Renal processes 1. Glomerular filtration From the blood, protein-free plasma (20%) is filtered through the renal corpuscle (consists of the Bowman capsule and glomerulus) at a rate of 125 mL min-1 - this rate is known as glomerular filtration rate (GFR) 2. Tubular reabsorption Substances of value (like glucose) are reabsorbed in the renal tubules 3. Tubular secretion Organic acids and bases are secreted into the urine at the proximal convoluted tubule  Renal processes 1. Glomerular Filtration 2. Tubular H20 Na+ 3. Tubular Reabsorption Secretion Source – A McNeilly lecture 2022 Renal glucose handling 1. Reabsorption of glucose (via Sodium GLucose coTransporters (SGLTs). 2. Release of glucose into the circulation via gluconeogenesis. 3. Uptake of glucose from circulation to satisfy its energy needs. Gluconeogenesis in the kidney Gluconeogenesis synthesis of new glucose from non-carbohydrate sources e.g. lactate, amino acids and glycerol Mediated by glucose-6-phosphatase (G-6-P) Occurs mostly in the liver Hepatic contribution (75-80%) Renal contribution (20-25%) Glycogenolysis (45-50%) Glycogenolysis (0%) Gluconeogenesis (25-30%) Gluconeogenesis (20-25%) Filtration rate of glucose All plasma glucose is filtered by the kidneys The filtration rate of glucose describes the amount of glucose filtered by the kidneys Glucose filtration is proportional to the plasma glucose concentration Higher plasma glucose concentration = higher glucose filtration rate  Glucose titration studies Glucose is single biochemical fuel source of both neurons and retina Therefore, renal glucose filtering must be balanced by renal glucose reabsorption Renal glucose handling can be measured clinically Glucose titration study In uncontrolled Diabetes, plasma glucose concentrations exceed reabsorption capacity and patients experience glucose in urine (glucosuria), increased volume of urine (polyuria) and increases thirst (polydipsia) Adapted from Medical Physiology, 3e, 2017 Glucose reabsorption by SGLT’s 6 members of the SGLT family: SGLT1 SGLT2 1 , 2, 4, 5, 6 and SMIT1 Site Intestine, Kidney Kidney Renal location Late proximal tubule Early proximal tubule (S3) (S1) Sugar specificity Glucose and Glucose galactose Glucose affinity High (Km=0.4mM) Low (Km=2mM) Glucose transport Low High capacity Renal glucose Approx. 10% Approx. 90% reabsorption (%) Role Dietary absorption of Renal glucose glucose and reabsorption. Inhibition galactose, renal of SGLT2 offers glucose reabsorption treatment for T2DM  Glucose reabsorption by SGLT’s Adapted from Medical Physiology, 3e, 2017  SGLT2 inhibitors for type 2 Diabetes Mellitus (T2DM) Canagliflozin Dapagliflozin Empagliflozin Ertugliflozin Source – A McNeilly lecture 2022 Summary The kidneys’ role in glucose homeostasis occurs in 3 ways: Reabsorption of glucose. Release of glucose into the circulation via gluconeogenesis. Uptake of glucose from circulation to satisfy its energy needs. All become perturbed in T2D. SGLT2 inhibitors exploit the kidneys’ role in glucose reabsorption to reduce the level of glucose in the body. Thank you. Questions?