Gestational Diabetes Is Characterized by Reduced Mitochondrial Protein Expression and Altered Calcium Signaling Proteins in Skeletal Muscle

• Published in: PloS one Vol. 9; no. 9; p. e106872
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.09.2014; Public Library of Science (PLoS)
• Subjects: Adenylate Kinase - metabolism; Adult; Biology and Life Sciences; Calcineurin; Calcium; Calcium homeostasis; Calcium Signaling; Calcium signalling; Cardiomyopathy; Dehydrogenases; Diabetes; Diabetes mellitus; Diabetes, Gestational - metabolism; Electron Transport; Electron transport chain; Enzymatic activity; Female; Fetuses; Gene expression; Gestational diabetes; Glucose; Glucose tolerance; Glucose Tolerance Test; Gynecology; Homeostasis; Hospitals; Humans; Insulin resistance; Lipid peroxidation; Lipids; Maternal & child health; Medicine; Medicine and Health Sciences; Metabolism; Mitochondria; Mitochondria - enzymology; Mitochondrial Proteins - metabolism; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; NADH-ubiquinone oxidoreductase; Obesity; Obesity - metabolism; Obstetrics; Oxidation; Oxidative phosphorylation; Pathogenesis; Pediatrics; Phosphorylation; Physical activity; Postpartum; Preeclampsia; Pregnancy; Proteins; Proteomics; Public health; Regulators; Risk analysis; Risk factors; Rodents; Skeletal muscle; Womens health; Victoria Australia; Australia; United States > US; Colorado; Arizona
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106872

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, α1-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 (-60-75%) 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.