Activin A Levels Are Associated With Abnormal Glucose Regulation in Patients With Myocardial Infarction

Potential Counteracting Effects of Activin A on Inflammation

  1. Pål Aukrust4,7,8
  1. 1Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway
  2. 2Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway
  3. 3Center for Heart Failure Research, University of Oslo, Oslo, Norway
  4. 4Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  5. 5Section of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway
  6. 6Section for Transplantation and Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway
  7. 7Faculty of Medicine, University of Oslo, Oslo, Norway
  8. 8Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
  1. Corresponding author: Geir Øystein Andersen, medisin.uio.no/gend{at}uus.no.
  1. T.U. and E.C.K. contributed equally to this work.

Abstract

OBJECTIVE On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI).

RESEARCH DESIGN AND METHODS Activin A measurement and oral glucose tolerance tests (OGTTs) were performed in patients (n = 115) with acute MI, without previously known diabetes, and repeated after 3 months. Release of activin A and potential anti-inflammatory effects of activin A were measured in human endothelial cells. Activin A effects on insulin secretion and inflammation were tested in human pancreatic islet cells.

RESULTS 1) In patients with acute MI, serum levels of activin A were significantly higher in those with abnormal glucose regulation (AGR) compared with those with normal glucose regulation. Activin A levels were associated with the presence of AGR 3 months later (adjusted odds ratio 5.1 [95% CI 1.73–15.17], P = 0.003). 2) In endothelial cells, glucose enhanced the release of activin A, whereas activin A attenuated the release of interleukin (IL)-8 and enhanced the mRNA levels of the antioxidant metallothionein. 3) In islet cells, activin A attenuated the suppressive effect of inflammatory cytokines on insulin release, counteracted the ability of these inflammatory cytokines to induce mRNA expression of IL-8, and induced the expression of transforming growth factor-β.

CONCLUSIONS We found a significant association between activin A and newly detected AGR in patients with acute MI. Our in vitro findings suggest that this association represents a counteracting mechanism to protect against inflammation, hyperglycemia, and oxidative stress.

Footnotes

    • Received October 24, 2010.
    • Accepted January 27, 2011.

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    1. Diabetes vol. 60 no. 5 1544-1551
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