Activin A Levels Are Associated With Abnormal Glucose Regulation in Patients With Myocardial Infarction: Potential Counteracting Effects of Activin A on Inflammation.
Andersen, Geir O. 1,2,3,; Ueland, Thor 4,5; Knudsen, Eva C. 1,2,3; Scholz, Hanne 6; Yndestad, Arne 3,4; Sahraoui, Afaf 6; Smith, Camilla 4; Lekva, Tove 4,5; Otterdal, Kari 4; Halvorsen, Bente 4,7; Seljeflot, Ingebjorg 1,2,3,7; Aukrust, Pal 4,7,8
[Miscellaneous Article]
Diabetes.
60(5):1544-1551, May 2011.
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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-[beta].
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.
(C) 2011 by the American Diabetes Association, Inc.
