PS-B09-10: CANAGLIFLOZIN, A SODUIM-GLUCOSE TRANSPORTER 2 INHIBITOR IMPROVES GLUCOCORTICOID-INDUCED CARDIAC AND RENAL LIPID MISHANDLING BY SUPPRESSING LACTATE PRODUCTION IN FEMALE RATS

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Evidence exist that lactate production has pathophysiological implications in the development of hyperinsulinemia-linked cardiac and renal dysfunctions. The cardio-renal protective effects of sodium-glucose co-transporter-2 inhibitor (SGLT2i) has not been associated with lactate production. The study therefore sought to test the hypothesis that SGLT2i would ameliorate insulin resistance and cardiorenal lipid mishandling by suppressing lactate production. Wistar female rats weighing between 140 and 160 g were randomly allotted into control, DEX and DEX+CANA groups (6 rats per group). The groups received (p.o.) vehicle (distilled water), dexamethasone (0.2 mg/kg) and and a combination of Dex with a SGLT2i (Canagliflozin; 10.0 mg/kg), respectively for a period of 6 days. Data showed that DEX exposure led to hyperinsulinemia, insulin resistance, elevated atherogenic plasma lipid index, accumulation of cardiac and renal triglyceride, free fatty acid, and increased lipid peroxidation in the hearts and kidneys as well as enhanced lactate production. However, the induced alterations by DEX were ameliorated by SGLT2i, CANA. Collectively, the present results demonstrate that glucocorticoid-linked hyperinsulinemia-mediated lipid mishandling in the heart and kidney is ameliorated by CANA, a SGLT2i. The implication of the findings of the study is that SGLT2i could reduce lipid accumulation in the hearts and kidneys, at least, by suppression of the lactate production