title: Activin A levels are associated with abnormal glucose regulation in patients with myocardial infarction: potential counteracting effects of activin A on inflammation.
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).
  
  
  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.
authors.affiliation: Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway. gend@uus.no
authors.forename: Geir Ø
authors.initials: GØ
authors.lastname: Andersen
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Eva C
authors.initials: EC
authors.lastname: Knudsen
authors.forename: Hanne
authors.initials: H
authors.lastname: Scholz
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Afaf
authors.initials: A
authors.lastname: Sahraoui
authors.forename: Camilla
authors.initials: C
authors.lastname: Smith
authors.forename: Tove
authors.initials: T
authors.lastname: Lekva
authors.forename: Kari
authors.initials: K
authors.lastname: Otterdal
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Seljeflot
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D028341:Activins / Q000097:blood*; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000097:blood* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; C422405:activin A; D028341:Activins