SGLT2 Inhibition Combined with Zn Supplementation Protects the Liver-Pancreas Axis in Experimental Type 2 Diabetes
4 affiliations
- 1Grigore T. Popa, University of Medicine and Pharmacy, Universitatii St. 16, 700115 Iasi, Romania
- 2Ion Ionescu de la Brad University of Life Sciences, Aleea Mihail Sadoveanu No. 3, 700490 Iasi, Romania
- 3Dunarea de Jos University, 800010 Galati, Romania
- 4University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
Abstract
Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia, inflammation, and progressive hepatic and pancreatic dysfunction. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors exert metabolic and organ-protective effects, their ability to preserve pancreatic architecture and attenuate diabetes-associated hepatic injury, particularly combined with nutritional interventions, remains insufficiently explored. This study investigated the protective effects of dapagliflozin (DAPA) and empagliflozin (EMPA), alone or combined with zinc (Zn), on hepatic and pancreatic alterations in experimental diabetes. Methods: Diabetes was induced in male Sprague–Dawley rats using streptozotocin (STZ) and high fat diet (HFD). Diabetic animals received DAPA, EMPA, Zn, or SGLT2 inhibitor–Zn combinations for four weeks. Hepatic biochemical parameters, lipid profile, histopathology, pancreatic morphometry, and insulin immunoreactivity were evaluated. Diabetes induced hepatic and pancreatic alterations, including elevated liver injury markers, hepatocellular degeneration, reduced islet number and β-cell density, and diminished insulin immunoreactivity. DAPA and EMPA attenuated these changes, with greater improvements following Zn combination therapy. EMPA + Zn produced the most favorable response, improving hepatic architecture, reducing VCAM-1, ICAM-1, and NF-κB expression, preserving islet morphology, increasing β-cell density, and enhancing insulin immunoreactivity. SGLT2 inhibitors attenuated diabetes-associated hepatic and pancreatic alterations in this experimental model, while Zn supplementation was associated with additional tissue-preserving effects, particularly when combined with EMPA. These findings support further investigation of combined SGLT2 inhibition and Zn supplementation as an experimental approach to diabetes-associated organ injury; however, their clinical relevance remains to be established.
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BibTeX
@article{anton2026sglt2,
title = {{SGLT2 Inhibition Combined with Zn Supplementation Protects the Liver-Pancreas Axis in Experimental Type 2 Diabetes}},
author = {Irina Claudia Anton and Carmen Solcan and Liliana Mititelu-Tartau and Cornelia Amalinei and Mihaela Poroch and Vladimir Poroch and Beatrice Rozalina Buca and Cosmin-Gabriel Tartau and Ana-Maria Pelin and Alexandra Jitareanu and Mihail Virgil Boldeanu and Gina Eosefina Botnariu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209067},
url = {https://www.mdpi.com/1422-0067/27/20/9067},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - SGLT2 Inhibition Combined with Zn Supplementation Protects the Liver-Pancreas Axis in Experimental Type 2 Diabetes
AU - Irina Claudia Anton
AU - Carmen Solcan
AU - Liliana Mititelu-Tartau
AU - Cornelia Amalinei
AU - Mihaela Poroch
AU - Vladimir Poroch
AU - Beatrice Rozalina Buca
AU - Cosmin-Gabriel Tartau
AU - Ana-Maria Pelin
AU - Alexandra Jitareanu
AU - Mihail Virgil Boldeanu
AU - Gina Eosefina Botnariu
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209067
UR - https://www.mdpi.com/1422-0067/27/20/9067
AB - Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia, inflammation, and progressive hepatic and pancreatic dysfunction. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors exert metabolic and organ-protective effects, their ability to preserve pancreatic architecture and attenuate diabetes-associated hepatic injury, particularly combined with nutritional interventions, remains insufficiently explored. This study investigated the protective effects of dapagliflozin (DAPA) and empagliflozin (EMPA), alone or combined with zinc (Zn), on hepatic and pancreatic alterations in experimental diabetes. Methods: Diabetes was induced in male Sprague–Dawley rats using streptozotocin (STZ) and high fat diet (HFD). Diabetic animals received DAPA, EMPA, Zn, or SGLT2 inhibitor–Zn combinations for four weeks. Hepatic biochemical parameters, lipid profile, histopathology, pancreatic morphometry, and insulin immunoreactivity were evaluated. Diabetes induced hepatic and pancreatic alterations, including elevated liver injury markers, hepatocellular degeneration, reduced islet number and β-cell density, and diminished insulin immunoreactivity. DAPA and EMPA attenuated these changes, with greater improvements following Zn combination therapy. EMPA + Zn produced the most favorable response, improving hepatic architecture, reducing VCAM-1, ICAM-1, and NF-κB expression, preserving islet morphology, increasing β-cell density, and enhancing insulin immunoreactivity. SGLT2 inhibitors attenuated diabetes-associated hepatic and pancreatic alterations in this experimental model, while Zn supplementation was associated with additional tissue-preserving effects, particularly when combined with EMPA. These findings support further investigation of combined SGLT2 inhibition and Zn supplementation as an experimental approach to diabetes-associated organ injury; however, their clinical relevance remains to be established.
SN - 1422-0067
ER -