Vella Max, Mohan Sneha, Christie Hannah, Bailey Kent R, Cobelli Claudio, Dalla Man Chiara, Matveyenko Aleksey, Egan Aoife M, Vella Adrian
Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA.
J Endocr Soc. 2024 Jul 9;8(8):bvae130. doi: 10.1210/jendso/bvae130. eCollection 2024 Jul 1.
Multiple common genetic variants have been associated with type 2 diabetes, but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes.
To characterize the effect of diabetes-associated genetic variation at rs10830963 in the locus on islet function in people without type 2 diabetes.
The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon, and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose, and Disposition Indices were measured using the oral minimal model.
The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN.
Two cohorts were utilized for this analysis: 1 cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of genotype at rs7903146 from the Mayo Biobank.
Two-hour, 7-sample OGTT.
Fasting, nadir, and integrated glucagon concentrations.
One or 2 copies of the G-allele at rs10830963 were associated with increased postchallenge glucose and glucagon concentrations compared to subjects with the CC genotype.
The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.
多种常见基因变异与2型糖尿病相关，但它们导致糖尿病的机制尚未完全明确。其中一个例子是某基因座的变异，这暗示褪黑素及其受体参与了2型糖尿病的发病机制。
在非2型糖尿病患者中，研究rs10830963位点与糖尿病相关的基因变异对胰岛功能的影响。
在一个由294名曾接受口服葡萄糖耐量试验（OGTT）的个体组成的队列中，检测rs10830963位点的基因变异与血糖、胰岛素、C肽、胰高血糖素以及胰岛素分泌和作用指标之间的关联。使用口服最小模型测量胰岛素敏感性、β细胞对葡萄糖的反应性和处置指数。
明尼苏达州罗切斯特市梅奥诊所临床研究与转化科。
本分析使用了两个队列：一个队列是根据之前参与奥尔姆斯特德县的一项基于人群的研究招募的。另一个队列是根据梅奥生物样本库中rs7903146的基因型招募的。
两小时、7个样本的OGTT。
空腹、最低点和综合胰高血糖素浓度。
与CC基因型受试者相比，rs10830963位点携带1个或2个G等位基因的个体在接受挑战后血糖和胰高血糖素浓度升高。
rs10830963对葡萄糖稳态和2型糖尿病易感性的影响可能部分通过α细胞功能的变化介导。
