CHARACTERIZATION OF INSULIN SECRETION IN NORMOGLYCEMIC INDIVIDUALS

血糖正常个体胰岛素分泌的特征

• 批准号: 7377671
• 负责人: Steven C Elbein
• 金额: $ 0.14万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377671
• 关键词: CHARACTERIZATION; INSULIN; SECRETION; NORMOGLYCEMIC; INDIVIDUALS

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. We propose that euglycemic individuals homozygous for the K23 variant (K/K) of the KCNJ11 gene will show decreased insulin secretion in response to rising glucose when compared with individuals homozygous for the E23 variant (E/E), that this effect will be more significant when accounting for insulin sensitivity, and that recently described indexes of pancreatic sensitivity to glucose will be decreased in K/K homozygotes. Secondarily, we propose that a similar effect will be observed in individuals heterozygous for the variant haplotype comprising the exon 18 silent variant and the intron 15 variant of ABCC8. We propose three aims to address these hypotheses. 1. Genotype members of Utah families who have been previously characterized for the ABCC8 variants for the E23K variant. These data will allow us to establish haplotypes between ABCC8 and KCNJ11, to establish the existence of linkage disequilibrium, and to test indexes based on oral glucose tolerance tests in family members. 2. Screen 180 individuals who are between the ages of 30 and 50 years by oral glucose tolerance test (OGTT) and KCNJ11 genotype to select 25 individuals who are homozygous for the E/E and K/K genotypes and matched on age, gender, family history of diabetes, and body fat. This aim will determine glucose tolerance differences between the three genotypes at codon 23: E/E, E/K, and K/K, as well as selecting individuals with normal glucose tolerance for aim 3. 3. Compare insulin sensitivity, insulin secretion (acute insulin response to glucose), maximum insulin response to arginine, insulin response to graded glucose infusion, and minimal model indexes of insulin secretion in 25 individuals with the E/E genotype and 25 individuals with the K/K genotype.

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。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。我们提出，kCNJ11基因的K23变体（k/k）纯合子将显示出胰岛素分泌减少，而与E23变体（e/e）的个体相比，葡萄糖的响应增加（e/e）将在计算胰岛素敏感性和GLUCETIS INDECES execriative Indeex Indeex Inseex Indeex execriative Indeex上更为重要，而Pancrive则更为重要。 K/K纯合子。其次，我们建议在杂合的个体中观察到类似的效果，该变体单倍型包含外显子18静音变体和ABCC8的内含子15变体。我们提出了三个目的，以解决这些假设。 1。犹他州家族的基因型成员，他们以前曾为E23K变体的ABCC8变体进行了特征。这些数据将使我们能够在ABCC8和KCNJ11之间建立单倍型，从而确定链接不平衡的存在，并基于家庭成员的口服葡萄糖耐受性测试来测试索引。 2。通过口服葡萄糖耐受性测试（OGTT）和KCNJ11基因型在30至50岁之间的屏幕180个个人，为E/E和K/K基因型纯合子选择25个个体，并与年龄，性别，性别，糖尿病的家族史以及体内脂肪相匹配。该目的将确定密码子23：E/E，E/K和K/K的三种基因型之间的葡萄糖耐量差异，以及选择具有正常葡萄糖耐受性的个体的目标3。3。比较胰岛素敏感性，胰岛素敏感性，胰岛素分泌（急性胰岛素对葡萄糖的反应），最大程度地介绍了胰岛素响应，胰岛素响应，胰岛素响应，胰岛素响应，胰岛素响应，胰岛素响应，胰岛素反应， 25个患有E/E基因型的个体和25个具有K/K基因型的个体的胰岛素分泌。