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胰岛淀粉样多肽(胰淀素):25例2型(非胰岛素依赖型)糖尿病患者中未发现异常前体序列的证据。

Islet amyloid polypeptide (amylin): no evidence of an abnormal precursor sequence in 25 type 2 (non-insulin-dependent) diabetic patients.

作者信息

Nishi M, Bell G I, Steiner D F

机构信息

Department of Biochemistry, Howard Hughes Medical Institute, University of Chicago, Illinois.

出版信息

Diabetologia. 1990 Oct;33(10):628-30. doi: 10.1007/BF00400208.

Abstract

Islet amyloid polypeptide is the major protein component of the islet amyloid of patients with Type 2 (non-insulin-dependent) diabetes mellitus. Since the synthesis of a structurally abnormal or mutant protein may contribute to the formation of amyloid deposits, we have examined the possibility that a mutant form of islet amyloid polypeptide or its precursor contributes to the formation of islet amyloid in Type 2 diabetic patients. We have sequenced the islet amyloid polypeptide precursor coding regions of the gene of 25 patients with Type 2 diabetes. Genomic DNA fragments corresponding to exon 2 and 3 of the islet amyloid polypeptide gene were amplified from patients' peripheral blood leucocyte DNAs using the polymerase chain reaction and specific oligonucleotide primer sets, and then directly sequenced. The nucleotide sequences of the amplified regions of both alleles of the islet amyloid polypeptide gene of these 25 patients were identical to one another and to the sequence of an islet amyloid polypeptide allele isolated from a human fetal liver genomic library. These findings suggest that a primary structural abnormality of islet amyloid polypeptide or its precursor is unlikely to play a significant role in the formation of islet amyloid in Type 2 diabetic patients.

摘要

胰岛淀粉样多肽是2型(非胰岛素依赖型)糖尿病患者胰岛淀粉样物质的主要蛋白质成分。由于结构异常或突变蛋白的合成可能促成淀粉样沉积物的形成,我们研究了胰岛淀粉样多肽的突变形式或其前体促成2型糖尿病患者胰岛淀粉样物质形成的可能性。我们对25例2型糖尿病患者的该基因的胰岛淀粉样多肽前体编码区进行了测序。使用聚合酶链反应和特异性寡核苷酸引物对,从患者外周血白细胞DNA中扩增出与胰岛淀粉样多肽基因外显子2和3对应的基因组DNA片段,然后直接测序。这25例患者的胰岛淀粉样多肽基因两个等位基因的扩增区域的核苷酸序列彼此相同,且与从人胎儿肝脏基因组文库中分离出的一个胰岛淀粉样多肽等位基因的序列相同。这些发现提示,胰岛淀粉样多肽或其前体的一级结构异常不太可能在2型糖尿病患者胰岛淀粉样物质的形成中起重要作用。

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