1881-P: The SGLT2 Inhibitor Dapagliflozin Improves Glucose Control and Enhances Liver Fatty Acid Oxidation and Ketone Body Formation in Insulin Resistant Obese Zucker Rats

• DOI: 10.2337/db19-1881-p
• Publication Date: 2019-06-05T01:47:33Z
• Authors: TOBIAS KROON; THERESE HAGSTEDT; ANN KJELLSTEDT; ANNA LINDBLOM; LARS LÖFGREN; JEREMIE BOUCHER; MARIA SÖRHEDE WIN...; DANIEL LINDEN; KRISTINA WALLENIUS
• Keywords: Dapagliflozin

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective treatments for improving glucose control and reducing cardiovascular events in patients with T2D. In the present study we examined metabolic effects of chronic treatment SGLT2i dapagliflozin obese insulin resistant Zucker rats. Three different studies were performed aims to assess: 1) liver CoA intermediates, 2) whole-body FA metabolism using a constant infusion 3H-palmitate 3) tissue-specific rates utilization storage 3H-labelled bromo-palmitate 14C-labelled palmitate, respectively. Four weeks (1 mg/kg/d p.o.) markedly increased glucosuria, reduced HbA1c fasting plasma levels pancreatic content compared vehicle treated Liver acetyl-CoA while malonyl-CoA/acetyl-CoA ratio was decreased following treatment, suggestive an oxidation. Treatment also HMG-CoA levels, intermediate ketone body formation, indicating that is diverted formation. This supported by β-hydroxybutyrate dapagliflozin-treated rats vehicle. Dapagliflozin resulted The oxidation subsequently found be driven increase utilization. conclusion, improves homeostasis enhances animals. These results suggest dapagliflozin-induced loss urine signals state liver, which leads production. Disclosure T. Kroon: Employee; Self; AstraZeneca. Hagstedt: None. A. Kjellstedt: Lindblom: L. Löfgren: J. Boucher: M. Sörhede Winzell: D. Linden: K. Wallenius: Stock/Shareholder;