Glycolytic lactate in diabetic kidney disease

被引：17

作者：

Darshi, Manjula ^{[1
]}

Kugathasan, Luxcia ^{[2
]}

Maity, Soumya ^{[1
]}

Sridhar, Vikas S. ^{[2
]}

Fernandez, Roman ^{[3
]}

Limonte, Christine P. ^{[4
]}

Grajeda, Brian I. ^{[5
]}

Saliba, Afaf ^{[1
]}

Zhang, Guanshi ^{[1
]}

Drel, Viktor R. ^{[1
]}

Kim, Jiwan J. ^{[1
]}

Montellano, Richard ^{[1
]}

Tumova, Jana ^{[1
]}

Montemayor, Daniel ^{[1
]}

Wang, Zhu ^{[3
]}

Liu, Jian-Jun ^{[6
]}

Wang, Jiexun ^{[6
]}

Perkins, Bruce A. ^{[2
]}

Lytvyn, Yuliya ^{[2
]}

Natarajan, Loki ^{[7
]}

Lim, Su Chi ^{[8
,9
,10
]}

Feldman, Harold ^{[11
,12
]}

Toto, Robert ^{[13
]}

Sedor, John R. ^{[14
]}

Patel, Jiten ^{[13
]}

Waikar, Sushrut S. ^{[15
]}

Brown, Julia ^{[16
]}

Osman, Yahya ^{[17
]}

He, Jiang ^{[18
]}

Chen, Jing ^{[19
]}

Reeves, W. Brian ^{[1
]}

Boer, Ian H. de ^{[4
]}

Roy, Sourav ^{[5
]}

Vallon, Volker ^{[20
,21
]}

Hallan, Stein ^{[22
,23
]}

Gelfond, Jonathan A. L. ^{[3
]}

Cherney, David Z. I. ^{[2
]}

Sharma, Kumar ^{[1
]}

机构：

[1] Univ Texas Hlth San Antonio, Ctr Precis Med, Dept Med, Div Nephrol, San Antonio, TX 78229 USA

[2] Univ Hlth Network, Dept Med, Div Nephrol, Toronto, ON, Canada

[3] Univ Texas Hlth San Antonio, Dept Populat Hlth Sci, San Antonio, TX USA

[4] Univ Washington, Sch Med & Publ Hlth, Seattle, WA USA

[5] Univ Texas Paso, Border Biomed Res Ctr, Dept Biol Sci, El Paso, TX USA

[6] Khoo Teck Puat Hosp, Clin Res Unit, Singapore, Singapore

[7] Univ Calif San Diego, Herbert Wertheim Sch Publ Hlth, La Jolla, CA USA

[8] Khoo Teck Puat Hosp, Clin Res Unit & Admiralty Med Ctr, Singapore, Singapore

[9] Natl Univ Singapore, Saw Swee Hock Sch Publ Heath, Singapore, Singapore

[10] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore

[11] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA

[12] Univ Penn, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA USA

[13] Univ Texas Southwestern Med Ctr, Dept Internal Med, Dallas, TX USA

[14] Cleveland Clin, Glickman Urol & Kidney & Lerner Res Inst, Cleveland, OH USA

[15] Boston Univ, Boston Med Ctr, Sch Med, Sect Nephrol, Boston, MA USA

[16] Univ Illinois, Dept Med, Div Nephrol, Chicago, IL USA

[17] Wayne State Univ, Dept Med, Div Nephrol, Detroit, MI USA

[18] Tulane Univ, Med Ctr, Sch Publ Hlth, New Orleans, LA USA

[19] Dept Med, Div Nephrol, New Orleans, LA USA

[20] Univ Calif San Diego, Dept Med, La Jolla, CA USA

[21] VA San Diego Healthcare Ctr, San Diego, CA USA

[22] Norwegian Univ Sci & Technol, Fac Med, Dept Clin & Mol Med, Trondheim, Norway

[23] St Olav Hosp, Dept Nephrol, Trondheim, Norway

来源：

JCI INSIGHT | 2024年 / 9卷 / 11期

基金：

加拿大健康研究院;

关键词：

RENAL-INSUFFICIENCY COHORT; GLYCATION END-PRODUCTS; GLOMERULAR HYPERFILTRATION; ACCUMULATION; ASSOCIATIONS; DYSFUNCTION; INHIBITION;

D O I：

10.1172/jci.insight.168825

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with ageand sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.

引用

页码：1 / 16

页数：16

共 51 条

[1]

CASTELLINO P, 1990, SEMIN NEPHROL, V10, P228

[2]

CHEN YDI, 1993, DIABETES METAB, V19, P348

[3] The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus [J].

Cherney, David Z. I. ;

Perkins, Bruce A. ;

Soleymanlou, Nima ;

Har, Ronnie ;

Fagan, Nora ;

Johansen, Odd Erik ;

Woerle, Hans-Juergen ;

von Eynatten, Maximilian ;

Broedl, Uli C. .

CARDIOVASCULAR DIABETOLOGY, 2014, 13

[4] The role of aberrant mitochondrial bioenergetics in diabetic neuropathy [J].

Chowdhury, Subir K. Roy ;

Smith, Darrell R. ;

Fernyhough, Paul .

NEUROBIOLOGY OF DISEASE, 2013, 51 :56-65

[5] Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy [J].

Czajka, Anna ;

Malik, Afshan N. .

REDOX BIOLOGY, 2016, 10 :100-107

[6] Crabtree effect in kidney proximal tubule cells via late-stage glycolytic intermediates [J].

Darshi, Manjula ;

Tumova, Jana ;

Saliba, Afaf ;

Kim, Jiwan ;

Baek, Judy ;

Pennathur, Subramaniam ;

Sharma, Kumar .

ISCIENCE, 2023, 26 (04)

[7] Lactate Elicits ER-Mitochondrial Mg2+ Dynamics to Integrate Cellular Metabolism [J].

Daw, Cassidy C. ;

Ramachandran, Karthik ;

Enslow, Benjamin T. ;

Maity, Soumya ;

Bursic, Brian ;

Novello, Matthew J. ;

Rubannelsonkumar, Cherubina S. ;

Mashal, Ayah H. ;

Ravichandran, Joel ;

Bakewell, Terry M. ;

Wang, Weiwei ;

Li, Kang ;

Madaris, Travis R. ;

Shannon, Christopher E. ;

Norton, Luke ;

Kandala, Soundarya ;

Caplan, Jeffrey ;

Srikantan, Subramanya ;

Stathopulos, Peter B. ;

Reeves, W. Brian ;

Madesh, Muniswamy .

CELL, 2020, 183 (02) :474-+

[8] Chronic Renal Insufficiency Cohort Study (CRIC): Overview and Summary of Selected Findings [J].

Denker, Matthew ;

Boyle, Suzanne ;

Anderson, Amanda H. ;

Appel, Lawrence J. ;

Chen, Jing ;

Fink, Jeffrey C. ;

Flack, John ;

Go, Alan S. ;

Horwitz, Edward ;

Hsu, Chi-yuan ;

Kusek, John W. ;

Lash, James P. ;

Navaneethan, Sankar ;

Ojo, Akinlolu O. ;

Rahman, Mahboob ;

Steigerwalt, Susan P. ;

Townsend, Raymond R. ;

Feldman, Harold I. .

CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2015, 10 (11) :2073-2083

[9] Isolation, Characterization, And High Throughput Extracellular Flux Analysis of Mouse Primary Renal Tubular Epithelial Cells [J].

Ding, Wen ;

Yousefi, Keyvan ;

Shehadeh, Lina A. .

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2018, (136)

[10] AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function [J].

Dugan, Laura L. ;

You, Young-Hyun ;

Ali, Sameh S. ;

Diamond-Stanic, Maggie ;

Miyamoto, Satoshi ;

DeCleves, Anne-Emilie ;

Andreyev, Aleksander ;

Quach, Tammy ;

Ly, San ;

Shekhtman, Grigory ;

Nguyen, William ;

Chepetan, Andre ;

Le, Thuy P. ;

Wang, Lin ;

Xu, Ming ;

Paik, Kacie P. ;

Fogo, Agnes ;

Viollet, Benoit ;

Murphy, Anne ;

Brosius, Frank ;

Naviaux, Robert K. ;

Sharma, Kumar .

JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (11) :4888-4899

← 1 2 3 4 5 6 →