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Erschienen in: Diabetologia 3/2014

01.03.2014 | Article

Matrix metalloproteinase 9 opposes diet-induced muscle insulin resistance in mice

verfasst von: Li Kang, Wesley H. Mayes, Freyja D. James, Deanna P. Bracy, David H. Wasserman

Erschienen in: Diabetologia | Ausgabe 3/2014

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Abstract

Aims/hypothesis

Increased extracellular matrix (ECM) collagen is a characteristic of muscle insulin resistance. Matrix metalloproteinase (MMP) 9 is a primary enzyme that degrades collagen IV (ColIV). As a component of the basement membrane, ColIV plays a key role in ECM remodelling. We tested the hypotheses that genetic deletion of MMP9 in mice increases muscle ColIV, induces insulin resistance in lean mice and worsens diet-induced muscle insulin resistance.

Methods

Wild-type (Mmp9 +/+) and Mmp9-null (Mmp9 −/−) mice were chow or high-fat (HF) fed for 16 weeks. Insulin action was measured by the hyperinsulinaemic–euglycaemic clamp in conscious weight-matched surgically catheterised mice.

Results

Mmp9 −/− and HF feeding independently increased muscle ColIV. ColIV in HF-fed Mmp9 −/− mice was further increased. Mmp9 −/− did not affect fasting insulin or glucose in chow- or HF-fed mice. The glucose infusion rate (GIR), endogenous glucose appearance (EndoRa) and glucose disappearance (Rd) rates, and a muscle glucose metabolic index (Rg), were the same in chow-fed Mmp9 +/+ and Mmp9 −/− mice. In contrast, HF-fed Mmp9 −/− mice had decreased GIR, insulin-stimulated increase in Rd and muscle Rg. Insulin-stimulated suppression of EndoRa, however, remained the same in HF-fed Mmp9 −/− and Mmp9 +/+ mice. Decreased muscle Rg in HF-fed Mmp9 −/− was associated with decreased muscle capillaries.

Conclusions/interpretation

Despite increased muscle ColIV, genetic deletion of MMP9 does not induce insulin resistance in lean mice. In contrast, this deletion results in a more profound state of insulin resistance, specifically in the skeletal muscle of HF-fed mice. These results highlight the importance of ECM remodelling in determining muscle insulin resistance in the presence of HF diet.
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Metadaten
Titel
Matrix metalloproteinase 9 opposes diet-induced muscle insulin resistance in mice
verfasst von
Li Kang
Wesley H. Mayes
Freyja D. James
Deanna P. Bracy
David H. Wasserman
Publikationsdatum
01.03.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 3/2014
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-013-3128-1

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