Dehydration and insulinopenia are necessary and sufficient for euglycemic ketoacidosis in SGLT2 inhibitor-treated rats

• Published in: Nature communications Vol. 10; no. 1; pp. 548 - 10
• Main Authors: Perry, Rachel J., Rabin-Court, Aviva, Song, Joongyu D., Cardone, Rebecca L., Wang, Yongliang, Kibbey, Richard G., Shulman, Gerald I.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 59; 631/443/319; 631/443/319/1642; 631/443/319/2723; 692/163/2743; Adipose tissue; Animals; Antidiabetics; Benzhydryl Compounds - adverse effects; Catecholamine; Catecholamines; Corticosterone; Dehydration; Dehydration - complications; Dehydration - pathology; Depletion; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - pathology; Diabetic ketoacidosis; Disease Models, Animal; Furosemide; Glucagon; Glucocorticoids - metabolism; Glucose; Glucose - metabolism; Glucose transport; Glucosides - adverse effects; Humanities and Social Sciences; Humans; Inhibitors; Insulin - metabolism; Ketoacidosis; Ketogenesis; Ketosis - chemically induced; Ketosis - etiology; Ketosis - pathology; Lipolysis; Lipolysis - drug effects; Liver - drug effects; Liver - metabolism; Male; multidisciplinary; Protein transport; Proteins; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-1 - metabolism; Rodents; Science; Science (multidisciplinary); Secretion; Sodium; Sodium-glucose cotransporter; Sodium-Glucose Transporter 2 Inhibitors - adverse effects

Sodium-glucose transport protein 2 (SGLT2) inhibitors are a class of anti-diabetic agents; however, concerns have been raised about their potential to induce euglycemic ketoacidosis and to increase both glucose production and glucagon secretion. The mechanisms behind these alterations are unknown. H...