Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Yingli JiaBaoxue Yang

Abstract

A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson's trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose...Continue Reading

Citations

Dec 6, 2019·Acta Pharmacologica Sinica·Xiao-Qiang GengBao-Xue Yang
Jul 10, 2019·Scientific Reports·Ryo ShibusawaMasanobu Yamada
May 14, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Zhenyao LuGuangji Wang
May 8, 2020·Journal of Diabetes Research·Ricardo Pereira-Moreira, Elza Muscelli
May 16, 2020·Drug Discovery Today·Frederikke E SembachLisbeth N Fink
Jul 17, 2021·Annual Review of Nutrition·Melissa InigoShawn C Burgess

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