{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:41:04Z","timestamp":1790487664140,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T00:00:00Z","timestamp":1472515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Suomen Akatemia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2016,9]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Obesity has been recognized as a state of subclinical inflammation resulting in a loss of insulin receptors and decreased insulin sensitivity. We here studied in\u00a0vivo<\/jats:italic> the role of circulating matrix metalloproteinase\u20108 (MMP<\/jats:styled-content>\u20108) among young healthy twin adults. Also, in\u00a0vitro<\/jats:italic> analysis of the cleavage of human insulin receptor (INSR<\/jats:styled-content>) by MMP<\/jats:styled-content>\u20108 was investigated as well its inhibition by doxycycline and other MMP<\/jats:styled-content>\u20108 inhibitor, Ilomastat\/GM<\/jats:styled-content>6001, which are broad\u2010spectrum MMP<\/jats:styled-content> inhibitors.<\/jats:p><\/jats:sec>Materials and methods<\/jats:title>We analysed serum MMP<\/jats:styled-content>\u20108 levels by a time\u2010resolved immunofluorometric assay in obese (n\u00a0<\/jats:italic>=\u00a0<\/jats:italic>34), overweight (n\u00a0<\/jats:italic>=\u00a0<\/jats:italic>76) and normal weight (n\u00a0<\/jats:italic>=\u00a0<\/jats:italic>130) twin individuals. The effect of MMP<\/jats:styled-content>\u20108 on INSR<\/jats:styled-content> and the effects of synthetic MMP<\/jats:styled-content>\u20108 inhibitors, doxycycline and Ilomastat\/GM<\/jats:styled-content>6001, were studied by SDS<\/jats:styled-content>\u2010PAGE<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>We found that in obese individuals relative to normal weight individuals, the serum MMP<\/jats:styled-content>\u20108 levels and MMP<\/jats:styled-content>\u20108\/TIMP<\/jats:styled-content>\u20101 ratio were significantly increased (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0\u00b70031 and P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0\u00b7031, respectively). Among normal weight and obese individuals, also smoking significantly increases serum MMP<\/jats:styled-content>\u20108 and MMP<\/jats:styled-content>\u20108\/TIMP<\/jats:styled-content>\u20101 ratio. In vitro,<\/jats:italic> we found that INSR<\/jats:styled-content> was degraded by MMP<\/jats:styled-content>\u20108 and this was inhibited by doxycycline and Ilomastat\/GM<\/jats:styled-content>6001.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Obesity associated with elevated circulating MMP<\/jats:styled-content>\u20108 found among young adults may contribute to progression of insulin resistance by cleaving INSR<\/jats:styled-content>. This INSR<\/jats:styled-content> cleavage by MMP<\/jats:styled-content>\u20108 can be inhibited by synthetic MMP<\/jats:styled-content>\u20108 inhibitors such as doxycycline. In addition to obesity, also smoking independently explained increased MMP<\/jats:styled-content>\u20108 levels. Our results suggest that MMP<\/jats:styled-content>\u20108 is an essential mediator in systemic subclinical inflammatory response in obesity, and a potential drug target.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12649","type":"journal-article","created":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T07:47:59Z","timestamp":1465890479000},"page":"757-765","source":"Crossref","is-referenced-by-count":67,"title":["Association of MMP<\/scp>\u20108 with obesity, smoking and insulin resistance"],"prefix":"10.1111","volume":"46","author":[{"given":"Anneli","family":"Lauhio","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Helsinki University Central Hospital Helsinki Finland"},{"name":"Clinicum University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esa","family":"F\u00e4rkkil\u00e4","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Helsinki University Central Hospital Helsinki 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