TY - JOUR
T1 - Suppression of cardiac phosphatidate phosphohydrolase 1 activity and lipin mRNA expression in Zucker diabetic fatty rats and humans with type 2 diabetes mellitus
AU - Burgdorf, Christof
AU - Hänsel, Laura
AU - Heidbreder, Marc
AU - Jöhren, Olaf
AU - Schütte, Frank
AU - Schunkert, Heribert
AU - Kurz, Thomas
PY - 2009/12/4
Y1 - 2009/12/4
N2 - Lipin functions in mammalian phospholipid biosynthesis through its phosphatidate phosphohydrolase 1 (PAP1) activity. Here, we studied cardiac PAP1 activity and lipin expression ex vivo in 8-month-old Zucker diabetic fatty (ZDF) rats and humans with type 2 diabetes mellitus undergoing open heart surgery for coronary bypass grafting. Compared to non-diabetic littermates (ZDF-fa/+), left ventricular PAP1 activity was 29% lower in diabetic ZDF-fa/fa rats. Left ventricular PAP1 activities were 2.1-fold (ZDF-fa/fa) and 3.6-fold (ZDF-fa/+) higher than the respective atrial activities, indicating marked differences in cardiac distribution of PAP1. PAP1 activity was highly related with cardiac lipin-1 and lipin-3 mRNA expression in ZDF rats (r = 0.99 and 0.96). Consistent with the findings in experimental animals, human atrial tissue displayed PAP1 activity that was 33% lower in those having diabetes than in non-diabetic controls. Accordingly, atrial lipin-1 and lipin-3 mRNA expression in diabetic patients was 50% and 59% lower as in non-diabetic patients, respectively. Insulin therapy increased both PAP1 activity and lipin mRNA expression in diabetic patients. We conclude that suppression of cardiac PAP1 activity/lipin expression may contribute to metabolic dysfunction of the diabetic heart.
AB - Lipin functions in mammalian phospholipid biosynthesis through its phosphatidate phosphohydrolase 1 (PAP1) activity. Here, we studied cardiac PAP1 activity and lipin expression ex vivo in 8-month-old Zucker diabetic fatty (ZDF) rats and humans with type 2 diabetes mellitus undergoing open heart surgery for coronary bypass grafting. Compared to non-diabetic littermates (ZDF-fa/+), left ventricular PAP1 activity was 29% lower in diabetic ZDF-fa/fa rats. Left ventricular PAP1 activities were 2.1-fold (ZDF-fa/fa) and 3.6-fold (ZDF-fa/+) higher than the respective atrial activities, indicating marked differences in cardiac distribution of PAP1. PAP1 activity was highly related with cardiac lipin-1 and lipin-3 mRNA expression in ZDF rats (r = 0.99 and 0.96). Consistent with the findings in experimental animals, human atrial tissue displayed PAP1 activity that was 33% lower in those having diabetes than in non-diabetic controls. Accordingly, atrial lipin-1 and lipin-3 mRNA expression in diabetic patients was 50% and 59% lower as in non-diabetic patients, respectively. Insulin therapy increased both PAP1 activity and lipin mRNA expression in diabetic patients. We conclude that suppression of cardiac PAP1 activity/lipin expression may contribute to metabolic dysfunction of the diabetic heart.
UR - http://www.scopus.com/inward/record.url?scp=70349947074&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.09.108
DO - 10.1016/j.bbrc.2009.09.108
M3 - Journal articles
C2 - 19799857
AN - SCOPUS:70349947074
SN - 0006-291X
VL - 390
SP - 165
EP - 170
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
