title: Increased collagen content in insulin-resistant skeletal muscle.
abstract: Oversupply and underutilization of lipid fuels are widely recognized to be strongly associated with insulin resistance in skeletal muscle. Recent attention has focused on the mechanisms underlying this effect, and defects in mitochondrial function have emerged as a potential player in this scheme. Because evidence indicates that lipid oversupply can produce abnormalities in extracellular matrix composition and matrix changes can affect the function of mitochondria, the present study was undertaken to determine whether muscle from insulin-resistant, nondiabetic obese subjects and patients with type 2 diabetes mellitus had increased collagen content. Compared with lean control subjects, obese and type 2 diabetic subjects had reduced muscle glucose uptake (P<0.01) and decreased insulin stimulation of tyrosine phosphorylation of insulin receptor substrate-1 and its ability to associate with phosphatidylinositol 3-kinase (P<0.01 and P<.05). Because it was assayed by total hydroxyproline content, collagen abundance was increased in muscle from not only type 2 diabetic patients but also nondiabetic obese subjects (0.26+/-0.05, 0.57+/-0.18, and 0.67+/- 0.20 microg/mg muscle wet wt, lean controls, obese nondiabetics, and type 2 diabetics, respectively), indicating that hyperglycemia itself could not be responsible for this effect. Immunofluorescence staining of muscle biopsies indicated that there was increased abundance of types I and III collagen. We conclude that changes in the composition of the extracellular matrix are a general characteristic of insulin-resistant muscle.
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Rachele
authors.initials: R
authors.lastname: Berria
authors.forename: Lishan
authors.initials: L
authors.lastname: Wang
authors.forename: Dawn K
authors.initials: DK
authors.lastname: Richardson
authors.forename: Jean
authors.initials: J
authors.lastname: Finlayson
authors.forename: Renata
authors.initials: R
authors.lastname: Belfort
authors.forename: Thongchai
authors.initials: T
authors.lastname: Pratipanawatr
authors.forename: Elena A
authors.initials: EA
authors.lastname: De Filippis
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Kashyap
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Mandarino
mesh_terms: D000328:Adult; D001706:Biopsy; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D014443:Tyrosine; D005947:Glucose; D006909:Hydroxyproline