Cellular Mechanisms for Insulin Resistance in Human Gestational Diabetes Mellitus

人类妊娠糖尿病胰岛素抵抗的细胞机制

• 批准号: 8003061
• 负责人: Kristen Elizabeth Boyle
• 金额: $ 4.76万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003061
• 关键词: Adult; Biopsy; Cesarean section; Chronic; Controlled Study; Development; Diabetes Mellitus; Epigenetic Process; Fetus; Gestational Diabetes; High Prevalence; Human; Hyperinsulinism; Impairment; In Vitro; Incidence; Insulin Resistance; Knowledge; Mitochondria; Molecular; Morbidity - disease rate; Mothers; Muscle; Muscle Fibers; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Patients; Postpartum Period; Predisposition; Pregnancy; Prevalence; Research; Risk; Skeletal Muscle; Time; United States; Woman; impaired glucose tolerance; insulin signaling; mitochondrial dysfunction; obesity in children; offspring; pregnant; prospective; public health relevance

DESCRIPTION (provided by applicant): Gestational diabetes mellitus (GDM) complicates 3-10% of all pregnancies and is increasing in incidence, yet little is known about the molecular mechanisms of the insulin resistance. It results in significant morbidity to both the mother and the fetus, including a 50% risk of developing type 2 diabetes mellitus in the mother, and a high prevalence of childhood obesity and adult type 2 diabetes in the offspring. This research will examine mechanisms of insulin resistance in mothers with GDM compared to pregnant controls by studying skeletal muscle insulin signaling and mitochondrial function in a longitudinal prospective manner in three groups of subjects. Lean pregnant, obese pregnant, and obese GDM patients will be studied during late pregnancy and again after delivery when diabetes and hyperinsulinemia subsides. Repeat muscle biopsies will be collected at the time of elective cesarean section and again at 6-8 weeks post-partum in order to examine whether or not impairments in insulin signaling and mitochondrial function persist postpartum. We hypothesize that women who continue to have impaired glucose tolerance postpartum will demonstrate a chronic detriment in mitochondrial function and insulin signaling, some features of which will persist in skeletal muscle myotubes in-vitro, allowing us to investigate potential epigenetic mechanisms for increased risk underlying the progression to type 2 diabetes. PUBLIC HEALTH RELEVANCE: The prevalence of obesity and insulin resistance is widespread in the United States, and only increasing. Obese, insulin resistant women are more susceptible to developing gestational diabetes during pregnancy and have greatly increased risk of developing type 2 diabetes post-partum. Mitochondrial dysfunction has been widely implicated in the development of skeletal muscle insulin resistance, although the cellular mechanisms remain unknown. By examining women with and without gestational diabetes during and following delivery, we may be able to more clearly define these mechanisms and their association with insulin resistance. This knowledge will not only provide valuable information regarding the insulin resistance of pregnancy but also the predisposition to type 2 diabetes in women who develop gestational diabetes.

描述（由申请人提供）：妊娠糖尿病（GDM）使所有妊娠的3-10％复杂化，并且发病率增加，但对胰岛素抵抗的分子机制知之甚少。它会导致母亲和胎儿的显着发病率，包括在母亲中患上2型糖尿病的50％风险，以及在后代中儿童肥胖症和成人2型糖尿病的高患病率。这项研究将通过在三组受试者中以纵向的前瞻性方式研究骨骼肌胰岛素信号传导和线粒体功能，从而研究GDM母亲的胰岛素抵抗机制。在怀孕后期，糖尿病和高胰岛素血症消退时，将在怀孕期间以及分娩后再次研究苗条的怀孕，肥胖的怀孕和肥胖的GDM患者。重复的肌肉活检将在选修剖宫产段时收集，并在产后6-8周再次收集，以检查胰岛素信号传导和线粒体功能是否损害是否持续存在。我们假设，在产后继续受损的葡萄糖耐受性的女性将表现出长期损害线粒体功能和胰岛素信号传导的损害，其中某些特征将持续存在骨架肌肉肌动物，从而使我们能够调查增加型号的型号型号的型号的表观遗传机制。 公共卫生相关性：肥胖和胰岛素抵抗的流行在美国很普遍，只有在增加。肥胖，耐胰岛素妇女在怀孕期间更容易患妊娠糖尿病，并大大增加了产后2型糖尿病的风险。线粒体功能障碍已广泛与骨骼肌胰岛素抵抗的发展有关，尽管细胞机制仍然未知。通过检查分娩期间和之后患有和没有妊娠糖尿病的妇女，我们可能能够更清楚地定义这些机制及其与胰岛素抵抗的关系。这些知识不仅将提供有关妊娠胰岛素抵抗的有价值信息，而且还将提供患妊娠糖尿病的女性2型糖尿病的倾向。