Related Experiment Video

Updated: May 21, 2025

Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance
14:01

Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance

Published on: July 22, 2011

14.5K

Direct Thrombin Inhibitors Suppress Type 1 Diabetes Development through PI3K/p-AKT Pathway

Ahmed G Alharbi1,2, Hussien M Ali1,3, Ahmed H Alhowail1

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia.

Current Molecular Pharmacology
|May 20, 2025
PubMed
Abstract

Insights

Coagulation cascade activation is linked to type-1 diabetes development via the PI3K/AKT pathway. Direct thrombin inhibitors like dabigatran show potential in preventing type-1 diabetes in high-risk individuals.

Area of Science:

  • Immunology
  • Hematology
  • Endocrinology

Background:

  • Type-1 diabetes (T1DM) is an autoimmune disease characterized by insulin deficiency and hyperglycemia.
  • The relationship between coagulation cascade activation and T1DM development is not well-established.

Purpose of the Study:

  • To investigate the role of the coagulation system in T1DM progression.
  • To evaluate the protective effects of dabigatran, a direct thrombin inhibitor, in a mouse model of streptozotocin (STZ)-induced T1DM.

Main Methods:

  • Mice were divided into four groups: control, dabigatran-treated, STZ-treated, and STZ + dabigatran.
  • Evaluated parameters included blood glucose, platelets, serum insulin, and pancreatic histopathology.
  • Investigated protein expressions (PI3K, p-Akt, insulin, fibrinogen) in pancreatic tissues using immunofluorescence.

Main Results:

  • STZ-induced T1DM mice showed increased fibrinogen, PI3K, and p-Akt expression, and thrombocytopenia.
  • STZ treatment reduced pancreatic insulin levels.
  • Dabigatran co-treatment normalized fibrinogen, PI3K, and p-Akt levels, increased platelet counts, and restored insulin expression.

Conclusions:

  • Coagulation cascade activation, mediated by the PI3K/AKT pathway, contributes to T1DM.
  • Direct antithrombin therapy, such as dabigatran, may offer a novel strategy for T1DM prevention in at-risk populations.
Keywords:
AKTDabigatranFibrinogenHyperglycemiaPI3KType 1 diabetes

More Related Videos

Regulatory T cells: Therapeutic Potential for Treating Transplant Rejection and Type I Diabetes16:26

Regulatory T cells: Therapeutic Potential for Treating Transplant Rejection and Type I Diabetes

Published on: August 20, 2007

5.7K
Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells06:27

Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells

Published on: May 6, 2013

16.7K

Related Concept Videos

Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
146
Diabetes Mellitus: Overview and Type I Subtype01:22

Diabetes Mellitus: Overview and Type I Subtype

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
2.3K
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
277
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.1K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.6K
Diabetes Mellitus: Type 2 and Gestational01:22

Diabetes Mellitus: Type 2 and Gestational

Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
2.1K