Leffert J D, Newgard C B, Okamoto H, Milburn J L, Luskey K L
Gifford Laboratories, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 75235.
Proc Natl Acad Sci U S A. 1989 May;86(9):3127-30. doi: 10.1073/pnas.86.9.3127.
Amyloid deposits in the islets of Langerhans of the pancreas are a common finding in non-insulin-dependent diabetes mellitus. The main protein constituent of these deposits is a 37-amino acid peptide known as amylin that resembles calcitonin gene-related peptide, a neuropeptide. We have isolated cDNA clones corresponding to the rat amylin precursor from an islet cDNA library and we show that this peptide is encoded in a 0.9-kilobase mRNA that is translated to yield a 93-amino acid precursor. The amylin peptide is bordered by dibasic residues, suggesting that it is proteolyzed like calcitonin gene-related peptide. The peptide sequences flanking the amylin sequence do not resemble the calcitonin gene-related peptide flanking sequences. RNA hybridization studies show that amylin mRNA is abundant in the islets of Langerhans but is not present in the brain or seven other tissues examined. Dietary changes, such as fasting or fasting and refeeding, have little effect on amylin mRNA expression. This tissue specificity suggests that amylin is involved in specific signaling pathways related to islet function.
胰腺胰岛中的淀粉样沉积物在非胰岛素依赖型糖尿病中很常见。这些沉积物的主要蛋白质成分是一种名为胰淀素的37个氨基酸的肽，它类似于神经肽降钙素基因相关肽。我们从胰岛cDNA文库中分离出了与大鼠胰淀素前体对应的cDNA克隆，并表明该肽由一个0.9千碱基的mRNA编码，该mRNA被翻译产生一个93个氨基酸的前体。胰淀素肽以双碱性残基为界，表明它像降钙素基因相关肽一样被蛋白水解。胰淀素序列两侧的肽序列与降钙素基因相关肽两侧的序列不同。RNA杂交研究表明，胰淀素mRNA在胰岛中丰富，但在大脑或其他七个检测的组织中不存在。饮食变化，如禁食或禁食后再喂食，对胰淀素mRNA表达影响很小。这种组织特异性表明胰淀素参与了与胰岛功能相关的特定信号通路。
