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Hyaluronan Accumulates with High Fat Feeding and Contributes to Insulin Resistance.
MedLine Citation:
PMID:  23349492     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Increased deposition of specific extracellular matrix (ECM) components is a characteristic of insulin resistant skeletal muscle. Hyaluronan (HA) is a major constituent of the ECM. The hypotheses that 1) HA content is increased in the ECM of insulin resistant skeletal muscle and 2) reduction of HA in the muscle ECM by long-acting pegylated human recombinant PH20 hyaluronidase (PEGPH20) reverses high fat (HF) diet-induced muscle insulin resistance were tested. We show that muscle HA was increased in HF diet induced obese (DIO) mice and that treatment of PEGPH20, which dose-dependently reduced HA in muscle ECM, decreased fat mass, adipocyte size, hepatic and muscle insulin resistance in DIO mice at 10mg/kg. Reduced muscle insulin resistance was associated with increased insulin signaling, muscle vascularization, and percent cardiac output to muscle rather than insulin sensitization of muscle per se. Dose response studies revealed that PEGPH20 dose-dependently increased insulin sensitivity in DIO mice with a minimally effective dose of 0.01mg/kg. PEGPH20 at doses of 0.1 and 1mg/kg reduced muscle HA to levels seen in chow-fed mice, decreased fat mass, and increased muscle glucose uptake. These findings suggest that ECM HA is a target for treatment of insulin resistance.
Authors:
Li Kang; Louise Lantier; Arion Kennedy; Jeffrey S Bonner; Wesley Mayes; Deanna Bracy; Louis Bookbinder; Alyssa Hasty; Curtis Thompson; David Wasserman
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Diabetes     Volume:  -     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Vanderbuilt University, Molecular Physiology and Biophysics, Light Hall 823, 2215 Garland Avenue, Nashville, Tennessee, United States.
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