Nutrition, Early Development and Glucose Metabolism

营养、早期发育和葡萄糖代谢

• 批准号: 7262601
• 负责人: Patricia Myriam Vuguin
• 金额: $ 12.68万
• 依托单位: MONTEFIORE MEDICAL CENTER (BRONX, NY)
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-07 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7262601
• 关键词: Acanthosis Nigricans; Adolescent; Adult; African American; Age; Animal Feed; Animal Model; Animals; B Cell Proliferation; B-Lymphocytes; Biological; Body Composition; Body fat; Body mass index; Caucasians; Caucasoid Race; Cell physiology; Cells; Child; Childhood; Condition; Consumption; Coupled; Data; Defect; Deposition; Development; Diabetes Mellitus; Diagnosis; Diet; Dietary Fats; Dyslipidemias; Eating; Energy Intake; Environment; Epidemic; Event; Fasting; Fat-Restricted Diet; Fatty acid glycerol esters; GLUT4 gene; Glucose Intolerance; Hormonal; Human; Hyperinsulinism; Hypertension; In Vitro; Individual; Insulin; Insulin Receptor; Insulin Resistance; Intake; Lead; Life; Longitudinal Studies; Macronutrients Nutrition; Metabolic; Metabolic syndrome; Modeling; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Nutrient; Obesity; Overweight; Pancreas; Patients; Physiological; Physiology; Pima Indian; Population; Proteins; Proto-Oncogene Proteins c-akt; Puberty; Race; Rate; Rattus; Receptor Signaling; Relative (related person); Research Personnel; Risk; Risk Factors; Rodent; Role; Satiation; Staging; Syndrome; Testing; Tyrosine Phosphorylation; Visceral; Week; Weight; Weight Gain; adipokines; day; energy density; feeding; follow-up; glucose metabolism; glucose tolerance; glucose transport; in vivo; insulin secretion; insulin sensitivity; nutrition; prevent; response; sex; subcutaneous

DESCRIPTION (provided by applicant): The past two decades have seen an explosive increase in the number adolescents, diagnosed with type diabetes mellitus (T2DM) worldwide. The initial manifestations of the new epidemic of T2DM at midpuberty are insulin resistance and obesity. Most children who develop T2DM do so during puberty. Puberty is a susceptible period characterized by a transient reduction in insulin sensitivity, compensated by an adjusted increase in pancreatic insulin secretion. Therefore, the investigators hypothesize that puberty induced insulin resistance exacerbates the deleterious effect of excessive fat consumption on both insulin action and insulin secretion which may be irreversible. To elucidate the mechanisms by which excess fat intake during puberty leads to T2DM the investigators will use a chronically catheterized rat model, which allows for a longitudinal assessment of factors that modulate insulin action and secretion during puberty. The investigators will also determine the response of these factors to alterations in the composition of the diet. These in vivo tests will be coupled with the in vitro analysis to determine alterations on the cellular mechanism of insulin action (insulin receptor signaling: glucose transport activity, levels of IRbeta, IRS-1, IRS-2, GLUT4 and p85a regulatory subunit of the PI3Kinase, AKT and adipokines, together with the levels of insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1). Because the capacity of the b-cell is closely associated with insulin action, the investigators will characterize the ability of the pancreatic b-cell to secrete insulin in vivo during fat excess. The investigators will determine if the defect in b-cell function is functional or structural. Understanding the biological events that take part in the development of insulin resistance and/or defective insulin secretion with increased fat intake during puberty may lead to the development of new strategies to prevent T2DM in the young population.

描述（由申请人提供）：过去二十年来，全球诊断为糖尿病类型（T2DM）的青少年数量增加了爆炸性的增加。 T2DM在中间植物中新流行病的最初表现是胰岛素抵抗和肥胖。大多数开发T2DM的孩子在青春期会这样做。青春期是一个易感周期，其特征是胰岛素敏感性的瞬时降低，通过调整后胰岛胰岛素分泌的调整增加来补偿。因此，研究人员假设青春期诱导的胰岛素抵抗会加剧过量消耗脂肪对胰岛素作用和胰岛素分泌的有害影响，这可能是不可逆转的。为了阐明青春期中过量脂肪摄入导致T2DM的机制，研究人员将使用长期导管的大鼠模型，该模型允许对调节青春期胰岛素作用和分泌的因子进行纵向评估。研究人员还将确定这些因素对饮食组成改变的反应。这些体内测试将与体外分析相结合，以确定胰岛素作用的细胞机制的改变（胰岛素受体信号传导：葡萄糖转运活性，IRBETA，IRBETA，IRS-1，IRS-2，GLUT4和p85a调节性亚基与Pi3kinkinase，Akt和脂肪动物的调节亚基的水平胰岛素受体和IRS-1）。由于B细胞的能力与胰岛素作用密切相关，因此研究人员将表征胰腺B细胞在脂肪过量过程中分泌体内胰岛素的能力。研究人员将确定B细胞函数中的缺陷是功能还是结构性。了解在青春期期间胰岛素抵抗和/或有缺陷的胰岛素分泌的生物学事件可能会导致制定新策略，以防止年轻人群中T2DM。

项目成果

Animal models for small for gestational age and fetal programming of adult disease.

小胎龄动物模型和成人疾病的胎儿编程。

• DOI: 10.1159/000100545
• 发表时间: 2007
• 期刊: Hormone research
• 作者: Vuguin,PatriciaM

Effects of genetics and in utero diet on murine pancreatic development.

• DOI: 10.1530/joe-14-0114
• 发表时间: 2014-08
• 期刊: The Journal of endocrinology
• 作者: Lin CL;Williams L;Seki Y;Kaur H;Hartil K;Fiallo A;Glenn AS;Katz EB;Charron MJ;Vuguin PM
• 通讯作者: Vuguin PM

Interventional studies for polycystic ovarian syndrome in children and adolescents.

• DOI: 10.2217/phe.09.69
• 发表时间: 2010-02-01
• 期刊: Pediatric health
• 作者: Vuguin, Patricia Myriam

Critical periods of increased fetal vulnerability to a maternal high fat diet.

• DOI: 10.1186/1477-7827-12-80
• 发表时间: 2014-08-18
• 期刊: Reproductive biology and endocrinology : RB&E
• 作者: Plata Mdel M;Williams L;Seki Y;Hartil K;Kaur H;Lin CL;Fiallo A;Glenn AS;Katz EB;Fuloria M;Charron MJ;Vuguin PM
• 通讯作者: Vuguin PM