Abstract | BACKGRUOUND:
Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states. METHODS: Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA ( siRNA), cultured in serum-free Dulbecco's modified Eagle's medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours. RESULTS: CONCLUSION: These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.
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Authors | Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Yu-Mi Lim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee |
Journal | Endocrinology and metabolism (Seoul, Korea)
(Endocrinol Metab (Seoul))
Vol. 39
Issue 1
Pg. 98-108
(Feb 2024)
ISSN: 2093-5978 [Electronic] Korea (South) |
PMID | 38171209
(Publication Type: Journal Article)
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Chemical References |
- AMP-Activated Protein Kinases
- Glucose
- Phosphoenolpyruvate Carboxykinase (ATP)
- Proto-Oncogene Proteins c-akt
- RNA, Small Interfering
- Sodium
- Sodium-Glucose Transporter 2
- Sodium-Glucose Transporter 2 Inhibitors
- SLC5A2 protein, human
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Topics |
- Humans
- AMP-Activated Protein Kinases
(metabolism)
- Diabetes Mellitus, Type 2
(drug therapy)
- Gluconeogenesis
(genetics)
- Glucose
- Phosphoenolpyruvate Carboxykinase (ATP)
(genetics, metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism, pharmacology, therapeutic use)
- RNA, Small Interfering
(genetics, metabolism, pharmacology)
- Signal Transduction
- Sodium
(metabolism, pharmacology, therapeutic use)
- Sodium-Glucose Transporter 2
(metabolism, pharmacology, therapeutic use)
- Sodium-Glucose Transporter 2 Inhibitors
(pharmacology, therapeutic use)
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