Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle

Kristen E. Boyle, Hyonson Hwang, Rachel C. Janssen, James M. DeVente, Linda A. Barbour, Teri L. Hernandez, Lawrence J. Mandarino, Martha Lappas, Jacob E. Friedman

    Research output: Contribution to journalArticle

    25 Citations (Scopus)

    Abstract

    The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM) and obese pregnant women with normal glucose tolerance (ONGT). Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I) subunits (NDUFS3, NDUFV2) and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, a1-syntrophin, annexin A4) in OGDM (n = 6) vs. ONGT (n = 6). Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (260-75%) in the OGDM (n = 8) compared with ONGT (n = 10) subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum.

    Original languageEnglish (US)
    Article numbere106872
    JournalPLoS One
    Volume9
    Issue number9
    DOIs
    StatePublished - Sep 1 2014

    Fingerprint

    gestational diabetes
    Calcium Signaling
    Gestational Diabetes
    Mitochondrial Proteins
    Medical problems
    Muscle
    skeletal muscle
    Skeletal Muscle
    protein synthesis
    pregnant women
    Calcium
    Pregnant Women
    NADH dehydrogenase (ubiquinone)
    Proteins
    oxidative phosphorylation
    proteins
    Oxidative Phosphorylation
    protein content
    Proteomics
    proteomics

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Boyle, K. E., Hwang, H., Janssen, R. C., DeVente, J. M., Barbour, L. A., Hernandez, T. L., ... Friedman, J. E. (2014). Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle. PLoS One, 9(9), [e106872]. https://doi.org/10.1371/journal.pone.0106872

    Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle. / Boyle, Kristen E.; Hwang, Hyonson; Janssen, Rachel C.; DeVente, James M.; Barbour, Linda A.; Hernandez, Teri L.; Mandarino, Lawrence J.; Lappas, Martha; Friedman, Jacob E.

    In: PLoS One, Vol. 9, No. 9, e106872, 01.09.2014.

    Research output: Contribution to journalArticle

    Boyle, KE, Hwang, H, Janssen, RC, DeVente, JM, Barbour, LA, Hernandez, TL, Mandarino, LJ, Lappas, M & Friedman, JE 2014, 'Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle', PLoS One, vol. 9, no. 9, e106872. https://doi.org/10.1371/journal.pone.0106872
    Boyle, Kristen E. ; Hwang, Hyonson ; Janssen, Rachel C. ; DeVente, James M. ; Barbour, Linda A. ; Hernandez, Teri L. ; Mandarino, Lawrence J. ; Lappas, Martha ; Friedman, Jacob E. / Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle. In: PLoS One. 2014 ; Vol. 9, No. 9.
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