Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1β in type 2 diabetes patients
Abstract Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve the clinical outcomes remain elusive. We evaluated whether empagliflozin, an SGLT2 inhibitor, a...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22083-6 |
| _version_ | 1798018204678750208 |
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| author | Haekyung Lee Hyoungnae Kim Jin Seok Jeon Hyunjin Noh Rojin Park Dong Won Byun Hye Jeong Kim Kyoil Suh Hyeong Kyu Park Soon Hyo Kwon |
| author_facet | Haekyung Lee Hyoungnae Kim Jin Seok Jeon Hyunjin Noh Rojin Park Dong Won Byun Hye Jeong Kim Kyoil Suh Hyeong Kyu Park Soon Hyo Kwon |
| author_sort | Haekyung Lee |
| collection | DOAJ |
| description | Abstract Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve the clinical outcomes remain elusive. We evaluated whether empagliflozin, an SGLT2 inhibitor, ameliorates mitochondrial dysfunction and inflammatory milieu of the kidneys in T2DM patients. We prospectively measured copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) and urinary interleukin-1β (IL-1β) in healthy volunteers (n = 22), in SGLT2 inhibitor-naïve T2DM patients (n = 21) at baseline, and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Both urinary mtDNA copy numbers and IL-1β levels were higher in the T2DM group than in healthy volunteers. Baseline copy numbers of serum mtCOX-3 in the T2DM group were lower than those in healthy volunteers. Empagliflozin induced marked reduction in both urinary and serum mtND-1 and mtCOX-3 copy numbers, as well as in urinary IL-1β. Empagliflozin could attenuate mitochondrial damage and inhibit inflammatory response in T2DM patients. This would explain the beneficial effects of SGLT2 inhibitors on cardiovascular and renal outcomes. |
| first_indexed | 2024-04-11T16:20:11Z |
| format | Article |
| id | doaj.art-94cb54a70e6c444facc2b773d7f7a4cf |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T16:20:11Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-94cb54a70e6c444facc2b773d7f7a4cf2022-12-22T04:14:24ZengNature PortfolioScientific Reports2045-23222022-11-0112111010.1038/s41598-022-22083-6Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1β in type 2 diabetes patientsHaekyung Lee0Hyoungnae Kim1Jin Seok Jeon2Hyunjin Noh3Rojin Park4Dong Won Byun5Hye Jeong Kim6Kyoil Suh7Hyeong Kyu Park8Soon Hyo Kwon9Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Seoul HospitalDivision of Nephrology, Department of Internal Medicine, Soonchunhyang University Seoul HospitalDivision of Nephrology, Department of Internal Medicine, Soonchunhyang University Seoul HospitalDivision of Nephrology, Department of Internal Medicine, Soonchunhyang University Seoul HospitalDepartment of Laboratory Medicine, Soonchunhyang University Seoul HospitalDivision of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Seoul HospitalDivision of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Seoul HospitalDivision of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Seoul HospitalDivision of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Seoul HospitalDivision of Nephrology, Department of Internal Medicine, Soonchunhyang University Seoul HospitalAbstract Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve the clinical outcomes remain elusive. We evaluated whether empagliflozin, an SGLT2 inhibitor, ameliorates mitochondrial dysfunction and inflammatory milieu of the kidneys in T2DM patients. We prospectively measured copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) and urinary interleukin-1β (IL-1β) in healthy volunteers (n = 22), in SGLT2 inhibitor-naïve T2DM patients (n = 21) at baseline, and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Both urinary mtDNA copy numbers and IL-1β levels were higher in the T2DM group than in healthy volunteers. Baseline copy numbers of serum mtCOX-3 in the T2DM group were lower than those in healthy volunteers. Empagliflozin induced marked reduction in both urinary and serum mtND-1 and mtCOX-3 copy numbers, as well as in urinary IL-1β. Empagliflozin could attenuate mitochondrial damage and inhibit inflammatory response in T2DM patients. This would explain the beneficial effects of SGLT2 inhibitors on cardiovascular and renal outcomes.https://doi.org/10.1038/s41598-022-22083-6 |
| spellingShingle | Haekyung Lee Hyoungnae Kim Jin Seok Jeon Hyunjin Noh Rojin Park Dong Won Byun Hye Jeong Kim Kyoil Suh Hyeong Kyu Park Soon Hyo Kwon Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1β in type 2 diabetes patients Scientific Reports |
| title | Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1β in type 2 diabetes patients |
| title_full | Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1β in type 2 diabetes patients |
| title_fullStr | Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1β in type 2 diabetes patients |
| title_full_unstemmed | Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1β in type 2 diabetes patients |
| title_short | Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1β in type 2 diabetes patients |
| title_sort | empagliflozin suppresses urinary mitochondrial dna copy numbers and interleukin 1β in type 2 diabetes patients |
| url | https://doi.org/10.1038/s41598-022-22083-6 |
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