Matrix remodeling and insulin resistanceApr. 10, 2014, 8:00 AM
by Will Fry
Genetic deletion of the matrix metalloproteinase-9 enzyme (MMP-9), when coupled with a high-fat diet, exacerbates muscle insulin resistance in a mouse model of type 2 diabetes, Li Kang, Ph.D., David Wasserman, Ph.D., and colleagues report in the March issue of Diabetologia.
The researchers previously reported that diet-induced insulin resistance in these mice is associated with increased deposition of the extracellular matrix protein collagen IV and decreased activity of MMP-9, which degrades collagen IV.
While reduced MMP-9 by itself did not cause insulin resistance, the current findings support the hypothesis that, in the presence of a high-fat diet, loss of MMP-9 function leads to increased matrix deposition in muscle tissue and “a more profound state” of insulin resistance.
The study highlights a role for extracellular matrix remodeling in the development of insulin resistance. It also provides a cautionary note to those developing inhibitors of matrix metalloproteinases for the treatment of cancer and other diseases – these drugs may have an adverse effect on insulin action.
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