Activin A Levels Are Associated With Abnormal Glucose Regulation in Patients With Myocardial Infarction
Potential Counteracting Effects of Activin A on Inflammation
- Geir Ø. Andersen1,2,3⇓,
- Thor Ueland4,5,
- Eva C. Knudsen1,2,3,
- Hanne Scholz6,
- Arne Yndestad3,4,
- Afaf Sahraoui6,
- Camilla Smith4,
- Tove Lekva4,5,
- Kari Otterdal4,
- Bente Halvorsen4,7,
- Ingebjørg Seljeflot1,2,3,7 and
- Pål Aukrust4,7,8
- 1Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway
- 2Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway
- 3Center for Heart Failure Research, University of Oslo, Oslo, Norway
- 4Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- 5Section of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway
- 6Section for Transplantation and Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway
- 7Faculty of Medicine, University of Oslo, Oslo, Norway
- 8Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Corresponding author: Geir Øystein Andersen, .
T.U. and E.C.K. contributed equally to this work.
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.
- Received October 24, 2010.
- Accepted January 27, 2011.
- © 2011 by the American Diabetes Association.
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