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Proposal of a novel diabetogenic mechanism involving the serpin PAI‐1
Author(s) -
Griffiths Sarah L.,
Grainger David J.
Publication year - 2006
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.20418
Subject(s) - serpin , metabolic syndrome , insulin resistance , proteases , diabetes mellitus , mechanism (biology) , obesity , serine , serine protease , biology , medicine , disease , coronary heart disease , endocrinology , bioinformatics , protease , gene , genetics , enzyme , biochemistry , philosophy , epistemology
Abstract 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. BioEssays 28: 629–641, 2006. © 2006 Wiley Periodicals, Inc.