Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle.
Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle.
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DOI：
10.1371/journal.pone.0106872
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Friedman JE
中科院分区：
文献类型：
--
作者：
Boyle KE;Hwang H;Janssen RC;DeVente JM;Barbour LA;Hernandez TL;Mandarino LJ;Lappas M;Friedman JE
妊娠期糖尿病（GDM）的患病率不断上升，影响了高达18%的孕妇，对母亲和婴儿造成了直接和长期的代谢后果。异常葡萄糖摄取和脂质氧化是GDM的标志性特征，促使我们使用探索性蛋白质组学方法来研究GDM肥胖孕妇（OGDM）和糖耐量正常的肥胖孕妇（ONGT）之间骨骼肌代谢差异的细胞机制。在第二组肥胖OGDM和ONGT孕妇中进行功能验证。在分娩时收集的腹直肌骨骼肌组织中的定量蛋白质组学分析显示，与ONGT（n = 6）相比，OGDM（n =6）中线粒体复合物I（C-I）亚基（NDUFS 3，NDUFV 2）的蛋白质含量降低，参与钙稳态/信号传导的蛋白质（钙调神经磷酸酶A，α1-突触素，膜联蛋白A4）含量改变。 随访分析显示，与ONGT（n = 10）受试者相比，OGDM（n=8）中线粒体复合物C-I、C-III和C-IV的酶活性降低（−60-75%），但线粒体复合物蛋白含量没有观察到差异。 线粒体生物合成和氧化磷酸化的上游调节因子在组间没有差异。然而，AMPK磷酸化在OGDM女性中显著降低了75%。这些数据表明，GDM与骨骼肌氧化磷酸化减少和钙稳态紊乱有关。这些关系值得进一步关注，因为它们可能代表GDM发展的新风险因素，并可能对GDM治疗策略和产后2型糖尿病预防的体力活动干预的有效性产生影响。
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.
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DOI：
10.1152/ajpendo.00124.2001
发表时间：
2002-03-01
影响因子：
5.1
作者：
Catalano, PM;Nizielski, SE;Friedman, JE
通讯作者：
Friedman, JE
影响因子：
15.9
作者：
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DOI：
10.1152/ajpregu.00310.2010
发表时间：
2010-09-01
影响因子：
2.8
作者：
Heerwagen, Margaret J. R.;Miller, Melissa R.;Friedman, Jacob E.
通讯作者：
Friedman, Jacob E.
影响因子：
7.7
作者：
Friedman, Jacob E.;Kirwan, John P.;Catalano, Patrick M.
通讯作者：
Catalano, Patrick M.
影响因子：
4.8
作者：
Guha, Manti;Srinivasan, Satish;Avadhani, Narayan G.
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Avadhani, Narayan G.