Stoffel M, Espinosa R, Le Beau M M, Bell G I
Howard Hughes Medical Institute, University of Chicago, Illinois.
Diabetes. 1993 Aug;42(8):1215-8. doi: 10.2337/diab.42.8.1215.
Glucagon-like peptide-1 is a fragment of proglucagon secreted by intestinal L-cells. It has potent glucose-dependent insulin secretory effects and also suppresses gastric acid secretion in the stomach. The biological actions of GLP-1 are mediated by the GLP-1 receptor, the structure of which has recently been determined. Defects in insulin secretion are a common feature of NIDDM and as such the GLP-1 receptor is a candidate for contributing to the development of this clinically and genetically heterogeneous disorder. As a first step in determining the role of the GLP-1 receptor in the development of NIDDM, we have isolated the human GLP-1 receptor gene and mapped it to chromosome 6, band p21.1, using the technique of fluorescence in situ hybridization. We also identified a simple tandem repeat DNA polymorphism in the human GLP-1 receptor gene of the form (TG)n. This DNA polymorphism has 14 alleles and a heterozygosity of > 0.8. We have used this DNA polymorphism to localize the GLP-1 receptor gene within the genetic map of the short arm of chromosome 6. This DNA polymorphism will facilitate genetic studies of the contribution of the GLP-1 receptor gene to impaired beta-cell function and NIDDM.
胰高血糖素样肽-1是肠道L细胞分泌的胰高血糖素原的一个片段。它具有强大的葡萄糖依赖性胰岛素分泌作用,还能抑制胃中的胃酸分泌。GLP-1的生物学作用由GLP-1受体介导,其结构最近已被确定。胰岛素分泌缺陷是非胰岛素依赖型糖尿病(NIDDM)的一个常见特征,因此GLP-1受体是导致这种临床和遗传异质性疾病发生的一个候选因素。作为确定GLP-1受体在NIDDM发生中作用的第一步,我们利用荧光原位杂交技术分离出了人类GLP-1受体基因,并将其定位到6号染色体p21.1带。我们还在人类GLP-1受体基因中鉴定出一种形式为(TG)n的简单串联重复DNA多态性。这种DNA多态性有14个等位基因,杂合度大于0.8。我们利用这种DNA多态性将GLP-1受体基因定位在6号染色体短臂的遗传图谱内。这种DNA多态性将有助于对GLP-1受体基因在β细胞功能受损和NIDDM中的作用进行遗传学研究。