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2000
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
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Abstract

Background

Diabetes mellitus type-1 is an immunological disease associated with low insulin release and hyperglycemia due to beta cell loss. No clear studies show the relationship between the coagulation cascade activation and diabetes mellitus type-1 development.

Objective

The present work aimed to clarify the function of the active coagulation system in the progression of diabetes mellitus type-1 (T1DM). Furthermore, the possible protective action of direct thrombin inhibitors (dabigatran) against T1DM caused by streptozotocin (STZ)-induced T1DM in mice model was examined.

Materials and Methods

Forty Balb/c male albino mice were distributed into four different groups, with 10 mice in each group: normal, dabigatran (DAB)-treated, STZ-treated, and STZ+DAB. Blood glucose, blood platelets, serum insulin, nuclear consistency, and pancreas histopathological changes were evaluated. Moreover, the expressions of PI3K, p-Akt, insulin, and fibrinogen were investigated in the pancreatic tissues via immunofluorescent technique.

Results

The findings displayed enhanced islet expression of fibrinogen, p-Akt, and PI3K proteins along with thrombocytopenia in STZ-injected mice when equated to control. Furthermore, treatment with STZ reduced pancreatic insulin expression. DAB and STZ-cotreatment significantly diminished pancreatic tissue expression of fibrinogen, PI3K, and p-AKT, as well as increased platelet counts and pancreatic insulin expression.

Conclusion

The evidence supported the activation of coagulation cascade in T1DM through the PI3K/AKT pathway. Using direct antithrombin therapy may open new avenues for T1DM prevention in high-risk diabetes individuals.

© 2024 The Author(s).
© 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2024-01-01
2025-09-28

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Direct Thrombin Inhibitors Suppress Type 1 Diabetes Development through PI3K/p-AKT Pathway
Curr Mol Pharmacol 17, E18761429374852 (2024); https://doi.org/10.2174/0118761429374852250305153445
/content/journals/cmp/10.2174/0118761429374852250305153445
/content/journals/cmp/10.2174/0118761429374852250305153445
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  • Article Type:     Research Article
Keyword(s): AKT; Dabigatran; Fibrinogen; Hyperglycemia; PI3K; Type 1 diabetes

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