期刊
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
卷 117, 期 2, 页码 83-87出版社
JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH
DOI: 10.1055/s-2008-1078733
关键词
type 2 diabetes; genetic association study; procolipase; insulin secretion; insulin sensitivity; enterostatin
资金
- Deutsche Forschungsgemeinschaft [KFO 114/1]
- EU-TMR Networks [CT1997-00142]
- fortune project [F1284282]
Aims: Procolipase (CLPS) is secreted from the exocrine pancreas into the gastrointestinal tract and becomes proteolytically cleaved into colipase and the pentapeptide enterostatin. While colipase is an indispensable cofactor for pancreatic lipase, enterostatin acts as a hormone that inhibits insulin secretion and confers satiety signals to the brain, thereby restricting further food intake in animal models. As both high fat diet and obesity contribute to insulin resistance, we investigated whether genetic variability of CLPS associates with metabolic traits in non-diabetic humans at diabetes risk. Methods: Tagging single nucleotide polymorphisms (SNPs) in the human CLIPS locus on chr6p21.1 were selected using HapMap data. 498 humans, phenotyped for different glucose and lipid metabolic traits, were genotyped by bidirectional sequencing and multivariate linear regression analyses were undertaken. Results: 2 tagging SNPs (rs3748050 in the Kozak sequence: A/G and rs3748051 in intron 1: A/G), covering 100% of CLPS variability including 8 kb of its promoter, were genotyped for association analyses. The minor alleles of both tagging SNPs associated significantly with a reduced insulin secretion (- 20.2 %, both SNPs) in various estimation models derived from the oral glucose tolerance test (OGTT; rs3748050/51: 30 min C-peptide levels: p=0.001/0.01, insulinogenic index: p=0.02/0.02, AUC C-peptide/AUC glucose: p = 0.01/0.01) after adjustment for relevant covariates. No significant associations with fasting total cholesterol (c), HDL-c, LDL-c, triglycerides and free fatty acids were found (all p > 0.11). Conclusions: CLPS genetic variability associates with insulin secretory function in non-diabetic humans and may represent a novel candidate gene for development of type 2 diabetes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据