Journal article
Insulin Resistance in Striated Muscle-specific Integrin Receptor β1-deficient Mice
The Journal of biological chemistry, Vol.284(7), pp.4679-4688
02/13/2009
DOI: 10.1074/jbc.M807408200
PMCID: PMC2640962
PMID: 19064993
Abstract
Integrin receptor plays key roles in mediating both inside-out and
outside-in signaling between cells and the extracellular matrix. We have
observed that the tissue-specific loss of the integrin β1 subunit in
striated muscle results in a near complete loss of integrin β1 subunit
protein expression concomitant with a loss of talin and to a lesser extent, a
reduction in F-actin content. Muscle-specific integrin β1-deficient mice
had no significant difference in food intake, weight gain, fasting glucose,
and insulin levels with their littermate controls. However, dynamic analysis
of glucose homeostasis using euglycemichyperinsulinemic clamps demonstrated a
44 and 48% reduction of insulin-stimulated glucose infusion rate and glucose
clearance, respectively. The whole body insulin resistance resulted from a
specific inhibition of skeletal muscle glucose uptake and glycogen synthesis
without any significant effect on the insulin suppression of hepatic glucose
output or insulin-stimulated glucose uptake in adipose tissue. The reduction
in skeletal muscle insulin responsiveness occurred without any change in GLUT4
protein expression levels but was associated with an impairment of the
insulin-stimulated protein kinase B/Akt serine 473 phosphorylation but not
threonine 308. The inhibition of insulin-stimulated serine 473 phosphorylation
occurred concomitantly with a decrease in integrin-linked kinase expression
but with no change in the mTOR·Rictor·LST8 complex (mTORC2).
These data demonstrate an
in vivo
crucial role of integrin β1
signaling events in mediating cross-talk to that of insulin action.
Details
- Title: Subtitle
- Insulin Resistance in Striated Muscle-specific Integrin Receptor β1-deficient Mice
- Creators
- Haihong Zong - Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461Claire C Bastie - Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461Jun Xu - Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461Reinhard Fassler - Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461Kevin P Campbell - Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461Irwin J Kurland - Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461Jeffrey E Pessin - Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.284(7), pp.4679-4688
- DOI
- 10.1074/jbc.M807408200
- PMID
- 19064993
- PMCID
- PMC2640962
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology
- Language
- English
- Date published
- 02/13/2009
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020799402771
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