Proposal of a novel diabetogenic mechanism involving the serpin PAI-1.
Metabolic Syndrome is a cluster of risk factors (including obesity, hypertension and insulin resistance), which is associated with late-onset diabetes and coronary heart disease. Elevated levels of the protease inhibitor PAI-1 are well-known molecular markers of the Metabolic Syndrome. Here, however, we present a hypothesis that PAI-1 acts as a causative factor in the development of Metabolic Syndrome and its clinical sequelae. We propose that PAI-1 inhibits the activity of members of the proprotein convertase (PC) class of serine proteases and that this underlies, at a molecular level, many of the other features of the Metabolic Syndrome cluster.
Griffiths
Sarah L
SL
Department of Medicine, University of Cambridge, UK.
Grainger
David J
DJ
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D013379:Substrate Specificity; D013577:Syndrome; D013917:Thrombin / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D015843:Serpins; D013917:Thrombin