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). 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.

journal_name

Diabetes

journal_title

Diabetes

authors

Andersen GØ,Ueland T,Knudsen EC,Scholz H,Yndestad A,Sahraoui A,Smith C,Lekva T,Otterdal K,Halvorsen B,Seljeflot I,Aukrust P

doi

10.2337/db10-1493

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

1544-51

issue

5

eissn

0012-1797

issn

1939-327X

pii

db10-1493

journal_volume

60

pub_type

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