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Updated: Aug 14, 2026

Leprdb Mouse Model of Type 2 Diabetes: Pancreatic Islet Isolation and Live-cell 2-Photon Imaging Of Intact Islets
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Leprdb Mouse Model of Type 2 Diabetes: Pancreatic Islet Isolation and Live-cell 2-Photon Imaging Of Intact Islets

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Platelet inhibition by insulin is absent in type 2 diabetes mellitus

Irlando Andrade Ferreira1, Astrid I M Mocking, Marion A H Feijge

  • 1Department of Hematology, University Medical Center Utrecht, Utrecht University, The Netherlands.

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 13, 2005
PubMed
Abstract

Insights

Patients with type 2 diabetes mellitus (DM2) exhibit hyperactive platelets due to a loss of insulin responsiveness and increased P2y12 signaling. This contributes to heightened adhesion and aggregation, impacting thrombus formation.

Area of Science:

  • Cardiovascular Biology
  • Metabolic Disorders
  • Platelet Physiology

Background:

  • ADP-induced P2y12 signaling is vital for arterial thrombus stability.
  • Insulin normally inhibits platelet activation by blocking Gi-protein signaling and suppressing cAMP.
  • Platelet dysfunction is a known complication in type 2 diabetes mellitus (DM2).

Purpose of the Study:

  • To investigate the effect of insulin on platelet function in patients with type 2 diabetes mellitus (DM2).
  • To determine if insulin resistance in platelets contributes to their hyperactivity in DM2.

Main Methods:

  • Assessed insulin signaling in platelets from healthy subjects and DM2 patients using Ser473 phosphorylation of protein kinase B.
  • Measured platelet adhesion, aggregation, and procoagulant activity upon collagen stimulation.
  • Evaluated P2y12-mediated suppression of cAMP and inhibition by AR-C69931MX in DM2 platelets.

Main Results:

  • Platelets from DM2 patients showed a complete loss of responsiveness to insulin, unlike normal platelets which had a 2-fold increase in insulin signaling.
  • DM2 platelets exhibited increased adhesion, aggregation, and procoagulant activity when stimulated with collagen.
  • DM2 platelets displayed enhanced P2y12-mediated suppression of cAMP and reduced inhibition by AR-C69931MX.

Conclusions:

  • The loss of platelet insulin responsiveness in DM2 contributes to platelet hyperactivity.
  • Increased P2y12 signaling in DM2 platelets exacerbates their hyperactive state.
  • These findings offer a molecular explanation for increased thrombotic risk in type 2 diabetes.

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