Activin A Levels Are Associated With Abnormal Glucose Regulation in Patients With Myocardial Infarction Potential Counteracting Effects of Activin A on Inflammation

作者：Andersen Geir O^*; Ueland Thor; Knudsen Eva C; Scholz Hanne; Yndestad Arne; Sahraoui Afaf; Smith Camilla; Lekva Tove; Otterdal Karl; Halvorsen Bente; Seljeflot Ingebjorg; Aukrust Pal

来源：Diabetes, 2011, 60(5): 1544-1551.

DOI：10.2337/db10-1493

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. Diabetes 60:1544-1551, 2011

• 出版日期2011-5