Interactive Effects of Empagliflozin and Hyperglycemia on Urinary Amino Acids in Individuals With Type 1 Diabetes.

Autor:	Kugathasan L; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.; Cardiovascular Sciences Collaborative Specialization, University of Toronto, Toronto, Ontario, Canada., Sridhar VS; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada., Lovblom LE; Biostatistics Department, University Health Network, Toronto, Ontario, Canada., Matta S; Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX.; Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, TX., Saliba A; Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX.; Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, TX., Debnath S; Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX.; Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, TX., AlAkwaa FM; Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI., Nair V; Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI., Bjornstad P; Division of Nephrology, Department of Medicine, University of Colorado, Aurora, CO.; Section of Endocrinology, Department of Pediatrics, University of Colorado, Aurora, CO., Kretzler M; Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI., Perkins BA; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.; Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada., Sharma K; Center for Precision Medicine, University of Texas Health San Antonio, San Antonio, TX.; Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, TX., Cherney DZI; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.; Cardiovascular Sciences Collaborative Specialization, University of Toronto, Toronto, Ontario, Canada.; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2024 Mar 01; Vol. 73 (3), pp. 401-411.
DOI:	10.2337/db23-0694
Abstrakt:	Optimizing energy use in the kidney is critical for normal kidney function. Here, we investigate the effect of hyperglycemia and sodium-glucose cotransporter 2 (SGLT2) inhibition on urinary amino acid excretion in individuals with type 1 diabetes (T1D). The open-label ATIRMA trial assessed the impact of 8 weeks of 25 mg empagliflozin orally once per day in 40 normotensive normoalbuminuric young adults with T1D. A consecutive 2-day assessment of clamped euglycemia and hyperglycemia was evaluated at baseline and posttreatment visits. Principal component analysis was performed on urinary amino acids grouped into representative metabolic pathways using MetaboAnalyst. At baseline, acute hyperglycemia was associated with changes in 25 of the 33 urinary amino acids or their metabolites. The most significant amino acid metabolites affected by acute hyperglycemia were 3-hydroxykynurenine, serotonin, glycyl-histidine, and nicotinic acid. The changes in amino acid metabolites were reflected by the induction of four biosynthetic pathways: aminoacyl-tRNA; valine, leucine, and isoleucine; arginine; and phenylalanine, tyrosine, and tryptophan. In acute hyperglycemia, empagliflozin significantly attenuated the increases in aminoacyl-tRNA biosynthesis and valine, leucine, and isoleucine biosynthesis. Our findings using amino acid metabolomics indicate that hyperglycemia stimulates biosynthetic pathways in T1D. SGLT2 inhibition may attenuate the increase in biosynthetic pathways to optimize kidney energy metabolism. (© 2024 by the American Diabetes Association.)
Databáze:	MEDLINE
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