ArticleAmerican journal of physiology. Cell physiology2012
Regulation of the human Na+-dependent glucose cotransporter hSGLT2.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review.Journal of diabetes research · 2020Pooled it
- Gene-environment interaction modifies the association between hyperinsulinemia and serum urate levels through SLC22A12.The Journal of clinical investigation · 2025Trial
- Commemorating the National Institute of Diabetes and Digestive and Kidney Diseases' Advances in Kidney Health: 75 Years of Discovery and Impact.Journal of the American Society of Nephrology : JASN · 2026Article
- Signal Strength Aware Latent Spaces Reveal Molecularly Distinct Substructures within Human Kidney Tissue.bioRxiv : the preprint server for biology · 2026Article
- Fasting hijacks proximal tubule circadian control mechanisms to regulate glucose reabsorption via the Nrf1/Sglt2 pathway in mice.Nature communications · 2025Article
- Commemorating the National Institute of Diabetes and Digestive and Kidney Diseases' Advances in Kidney Health: 75 Years of Discovery and Impact.Clinical journal of the American Society of Nephrology : CJASN · 2025Article
- A lipid atlas of the human kidney.Science advances · 2025Article
- Coordinated Regulation of Renal Glucose Reabsorption and Gluconeogenesis by mTORC2 and Potassium.Journal of the American Society of Nephrology : JASN · 2025Article
- SGLT2 Inhibitors and Uric Acid Homeostasis.Gout, urate, and crystal deposition disease · 2024Article
- Regulatory Role of Fatty Acid Metabolism on Glucose-Induced Changes in Insulin and Glucagon Secretion by Pancreatic Islet Cells.International journal of molecular sciences · 2024Review
- Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects.The Journal of clinical endocrinology and metabolism · 2023Article
- Article
- Friend or Foe: Regulation, Downstream Effectors of RRAD in Cancer.Biomolecules · 2023Review
- Renoprotective Effects of SGLT2 Inhibitors.Heart failure clinics · 2022Review
- Changes in Proximal Tubular Reabsorption Modulate Microvascular Regulation via the TGF System.International journal of molecular sciences · 2022Review
- The sugar daddy: the role of the renal proximal tubule in glucose homeostasis.American journal of physiology. Cell physiology · 2022Review
- Cardiorenal Syndrome: The Role of Neural Connections Between the Heart and the Kidneys.Circulation research · 2022Review
- Insulin-induced mTOR signaling and gluconeogenesis in renal proximal tubules: A mini-review of current evidence and therapeutic potential.Frontiers in pharmacology · 2022Review
- A modular and reusable model of epithelial transport in the proximal convoluted tubule.PloS one · 2022Review
- Human Glucose Transporters in Renal Glucose Homeostasis.International journal of molecular sciences · 2021Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The human Na(+)-glucose cotransporter SGLT2 is expressed mainly in the kidney proximal convoluted tubule where it is considered to be responsible for the bulk of glucose reabsorption. Phosphorylation profiling has revealed that SGLT2 exists in a phosphorylated state in the rat renal proximal tubule cortex, so we decided to investigate the regulation of human SGLT2 (hSGLT2) by protein kinases. hSGLT2 was expressed in human embryonic kidney (HEK) 293T cells, and the activity of the protein was measured using radiotracer and whole cell patch-clamp electrophysiology assays before and after activation of protein kinases. 8-Bromo-adenosine cAMP (8-Br-cAMP) was used to activate protein kinase A, and sn-1,2-dioctanoylglycerol (DOG) was used to activate protein kinase C (PKC). 8-Br-cAMP stimulated D-[α-methyl-(14)C]glucopyranoside ([(14)C]α-MDG) uptake and Na(+)-glucose currents by 200% and DOG increased [(14)C]α-MDG uptake and Na(+)-glucose currents by 50%. In both cases the increase in SGLT2 activity was marked by an increase in the maximum rate of transport with no change in glucose affinity. These effects were completely negated by mutation of serine 624 to alanine. Insulin induced a 250% increase in Na(+)-glucose transport by wild-type but not S624A SGLT2. Parallel studies confirmed that the activity of hSGLT1 was regulated by PKA and PKC due to changes in the number of transporters in the cell membrane. hSGLT1 was relatively insensitive to insulin. We conclude that hSGLT1 and hSGLT2 are regulated by different mechanisms and suggest that insulin is an SGLT2 agonist in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.