Long-term administration of the α-amylase inhibitor acarbose effective against type 2 diabetes symptoms in C57BL/6 mice
Authors
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Natalya A. Borozdina
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
https://orcid.org/0000-0002-2320-655X
- Ekaterina N. Kazakova Branch of the State Scientific Centre Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
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Irina N. Gladkikh
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences
https://orcid.org/0000-0001-9668-319X
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Elena V. Leychenko
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences
https://orcid.org/0000-0002-2360-1365
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Igor A. Dyachenko
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
https://orcid.org/0000-0002-3053-2804
DOI:
https://doi.org/10.18413/rrpharmacology.10.455Abstract
Introduction: α-amylase inhibitors are an important class of second-line antihyperglycemic drugs. They slow down the breakdown and absorption of carbohydrates, reducing peak glucose concentration with meals. Recent reports have also shown other beneficial effects of α-amylase inhibitors on type 2 diabetes mellitus (T2DM).
Materials and Methods: T2DM was modeled by keeping C57BL/6 mice on a high-fat diet for 21 weeks. Starting at week 18, the animals were orally administered acarbose at a dose of 24 mg/kg or the comparative drug metformin at a dose of 200 mg/kg for 4 weeks. Body weight gain, visceral fat mass, and adipocyte diameter were monitored during the period of test substances administration. At weeks 17, 19 and 21 of the study, glucose tolerance starch test and insulin resistance test were performed, and fasting blood glucose was measured.
Results: Administration of acarbose for 2 and 4 weeks resulted in a significant reduction of postprandial glucose concentration in the starch test; glucose AUC was significantly lower after administration of acarbose at a dose of 24 mg/kg on the background of T2DM modeling. Acarbose at a dose of 24 mg/kg effectively reduced fasting glucose concentration after 2 and 4 weeks of daily treatment on par with metformin. Administration of acarbose at a dose of 24 mg/kg for 2 and 4 weeks resulted in a significant decrease in the glucose AUC in the insulin resistance test. Acarbose promoted a significant decrease in adipocyte diameter and body weight gain against the background of T2DM modeling.
Conclusion: Long-term acarbose administration at a daily dose of 24 mg/kg is effective in reducing postprandial glucose concentration in mice with T2DM due to its α-amylase inhibitory activity. Additionally, it can alleviate insulin resistance, lower fasting glucose concentration, and prevent obesity development by stimulating GLP-1 secretion.
Graphical Abstract
Keywords:
acarbose, α-amylase inhibitors, insulin resistance, type 2 diabetes mellitus, C57BL/6 miceReferences
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Copyright (c) 2024 Natalya A. Borozdin, Ekaterina N. Kazakova, Irina N. Gladkikh, Elena V. Leychenko, Igor A. Dyachenko
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