Adrenal gland-dependent augmentation of plasminogen activator inhibitor-1 expression in streptozotocin-induced diabetic mice.
BACKGROUND
Diabetes is associated with an excess risk of cardiac events, and one risk factor for infarction is an elevated level of plasminogen activator inhibitor-1 (PAI-1).


OBJECTIVE
To evaluate whether the glucocorticoid hormones are involved in the diabetes-induced PAI-1 production, we examined expression profiles of PAI-1 mRNA in adrenalectomized (ADX) mice with streptozotocin (STZ)-induced diabetes.


RESULTS
The diabetes-induced augmentation of plasma PAI-1 levels and PAI-1 mRNA expression in the heart and lungs was completely normalized in diabetic ADX mice. The glucocorticoid receptor antagonist RU486 significantly, but only partly suppressed PAI-1 induction in STZ-induced diabetic mice, suggesting that factors other than glucocorticoids are also involved in PAI-1 induction provoked by diabetes.


CONCLUSIONS
Our results suggested that the adrenal gland plays a critical role in the progression of thrombosis in diabetic patients by inducing expression of the PAI-1 gene.
Oishi
K
K
Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Ohkura
N
N
Ishida
N
N
D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000209:etiology; D005938:Glucocorticoids; D008168:Lung / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013311:Streptozocin; D013927:Thrombosis / Q000209:etiology; D015854:Up-Regulation / Q000235:genetics*
D005938:Glucocorticoids; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013311:Streptozocin