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August 1, 1994Diabetes

Insulin Increases Guanosine-3′ ,5′-Cyclic Monophosphate in Human Platelets: A Mechanism Involved in the Insulin Anti-Aggregating Effect

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Why the study?

Does insulin reduce platelet aggregability through modulation of cGMP concentrations in human platelets?

Population

Platelet-rich plasma (PRP) obtained from 17 healthy volunteers

Comparison

Incubation with human recombinant insulin for 3… vs Baseline or absence of specific inhibitors

Design

Preclinical

Follow-up

3 minutes (incubation time)

Authors

MTMariella TrovatiUniversity of CagliariPMPaola MassuccoOspedale San Luigi GonzagaLMLuigi MattielloPoliclinico Abano Terme

Discussion

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Implication

Supports insulin-cGMP signaling in animal platelets; leaves open human anti-aggregatory effects or clinical relevance.

Key Points

  • To determine whether insulin reduces platelet aggregability by modulating intracellular cyclic guanosine monophosphate (cGMP) concentrations.
  • Platelet-rich plasma (PRP) was obtained from 17 healthy volunteers and incubated for 3 minutes with recombinant human insulin at concentrations ranging from 0 to 1,920 pM.
  • cGMP concentrations were quantified by radioimmunoassay after 20-minute preincubations with genistein (10 µM), methylene blue (10 µM), IBMX (500 µM), or L-NMMA (30 µM).
  • Platelet aggregation in response to collagen and ADP was measured in PRP preincubated with or without the guanylate cyclase inhibitor methylene blue.
  • Insulin induced a dose-dependent increase in platelet cGMP from 18.5 ± 3.3 to 42.0 ± 6.4 pmol/10^9 platelets (P = 0.0001).
  • The cGMP increase was completely blunted by genistein and methylene blue, but remained significant following preincubation with IBMX (P = 0.003) and L-NMMA (P = 0.009).
  • Inhibition of platelet aggregation to collagen and ADP by insulin was completely abolished by preincubation with 10 µM methylene blue.

Structured PICO

Does insulin reduce platelet aggregability through modulation of cGMP concentrations in human platelets?

P
Population
Platelet-rich plasma (PRP) obtained from 17 healthy volunteers
I
Intervention
Incubation with human recombinant insulin (0 to 1,920 pM) for 3 minutes, with or without preincubation with inhibitors (genistein, methylene blue, IBMX, L-NMMA)
C
Comparator
Baseline (0 pM insulin) or absence of specific inhibitors
O
Outcome
cGMP concentrations in platelet-rich plasma and platelet aggregability to collagen and ADPsurrogate

Insulin exerts a platelet anti-aggregatory effect by increasing cGMP through direct receptor-mediated platelet guanylate cyclase activation.

Cite This Study

Trovati et al. (1994) studied this question.

synapsesocial.com/papers/6a82a84dd5d5076d1fb2873fhttps://doi.org/10.2337/diab.43.8.1015

Topics

Dual antiplatelet therapy
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Insulin Stimulates Nitric Oxide Synthesis in Human Platelets and, Through Nitric Oxide, Increases Platelet Concentrations of Both Guanosine-3′, 5′-Cyclic Monophosphate and Adenosine-3′, 5′-Cyclic Monophosphate1997 · 130 citations
  2. 2Insulin Directly Reduces Platelet Sensitivity to Aggregating Agents: Studies In Vitro and In Vivo1988 · 121 citations
  3. 3Restoration by insulin of impaired prostaglandin E1/I2 receptor activity of platelets in acute ischemic heart disease.1991 · 27 citations
  4. 4Studies on Mechanisms Involved in Hypoglycemia-Induced Platelet Activation1986 · 77 citations
  5. 5Platelet Resistance to Nitrates in Obesity and Obese NIDDM, and Normal Platelet Sensitivity to Both Insulin and Nitrates in Lean NIDDM1998 · 107 citations