GENETICS OF PANCREATIC FUNCTION IN THE DEVELOPMENT OF DIABETES MELLITUS

糖尿病发生过程中的胰腺功能遗传学

• 批准号: 7376923
• 负责人: KRISTI SILVER
• 金额: $ 0.79万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376923
• 关键词: GENETICS; PANCREATIC; FUNCTION; DEVELOPMENT; DIABETES

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 2 diabetes mellitus is one of the most common inherited diseases in man with an estimated prevalence in Caucasian populations of 8-10%. Current evidence suggests that the common forms of type 2 diabetes result from a number of predisposing genes, ech of which contributes modestly to the development of diabetes as well as aging and the environment. Type 2 diabetes is characterized by insulin resistance and beta cell dysfunction. Therefore, candidate genes for type 2 diabetes include those involved with insulin secretion. Genes known to affect insulin secretion and/or pancreatic development include pancreatic duodenal homeobox factor-1 (PDX-1), Beta2/NeuroD, insulin receptor substrate-2 (IRS-2) and the beta-3-adrenergic receptor (beta3AR). Functional mutations have been identified in these genes (PDX-1Asp76Asn, BETA2/NeuroD Ala45Thr, IRS2 Gly1057Asp, or beta3AR Trp64Arg) which have the potential to alter the function of the protein, thereby, individually or in combination, effecting insulin secretion. In this study, we propose to characterize insulin secretion in prospectively recruited age-gender- and BMI-matched nondiabetic subjects with either one or two of the following variants, PDX-1 Asp76Asn, BETA2/NeuroD Ala45Thr, IRS2 Gly1057Asp, or beta3AR Trp64Arg, using the frequently sampled intravenous glucose tolerance test (FSIGTT) and insulin oscillation studies and to determine if having two variants in genes related to beta cell function have additive effects on insulin secretion.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。2型糖尿病是人类最常见的遗传性疾病之一，估计在高加索人群中的患病率为8- 10%。目前的证据表明，2型糖尿病的常见形式是由许多易感基因引起的，其中许多基因对糖尿病的发展以及衰老和环境都有一定的影响。2型糖尿病的特征是胰岛素抵抗和β细胞功能障碍。因此，2型糖尿病的候选基因包括那些与胰岛素分泌有关的基因。已知影响胰岛素分泌和/或胰腺发育的基因包括胰腺十二指肠同源盒因子-1（PDX-1）、β 2/NeuroD、胰岛素受体底物-2（IRS-2）和β-3-肾上腺素能受体（β 3AR）。已在这些基因（PDX-1Asp 76 Asn、BETA 2/NeuroD Ala 45 Thr、IRS 2 Gly 1057 Asp或β 3AR Trp 64 Arg）中鉴定出功能突变，这些突变具有改变蛋白质功能的潜力，从而单独或联合影响胰岛素分泌。 在这项研究中，我们建议在前瞻性招募的年龄性别和BMI匹配的非糖尿病受试者中表征胰岛素分泌，这些受试者具有以下变体中的一种或两种：PDX-1 Asp 76 Asn、BETA 2/NeuroD Ala 45 Thr、IRS 2 Gly 1057 Asp或β 3AR Trp 64 Arg，使用频繁采样的静脉葡萄糖耐量试验（FSIGTT）和胰岛素振荡研究，并确定在与β细胞功能相关的基因中具有两种变体是否对胰岛素分泌具有累加效应。