Mulder H, Ahrén B, Sundler F
Department of Medical Cell Research, University of Lund, Sweden.
Mol Cell Endocrinol. 1995 Oct 30;114(1-2):101-9. doi: 10.1016/0303-7207(95)03646-o.
An increased ratio of islet amyloid polypeptide (IAPP) to insulin for mRNA and peptide content in pancreatic extracts and for secretion has been observed in experimental diabetes, suggesting a differentially regulated IAPP and insulin expression. Therefore, we investigated the islet expression of IAPP and insulin in streptozotocin and alloxan diabetic rats and mice, using in situ hybridization and immunocytochemistry. A low dose of streptozotocin equivalently reduced IAPP and insulin mRNA levels to approximately 45% of controls. In contrast, a high dose of streptozotocin or alloxan reduced IAPP mRNA levels significantly less than those of insulin mRNA (streptozotocin: 24 vs. 15%, P = 0.011; alloxan: 15 vs. 6%, P < 0.0001). In situ hybridization and immunocytochemistry revealed expression of IAPP in experimental diabetes to occur predominantly in insulin cells. Thus, IAPP and insulin gene expression are differentially regulated in experimental diabetes in rodents and IAPP is predominantly expressed in insulin cells.
在实验性糖尿病中,已观察到胰腺提取物中胰岛淀粉样多肽(IAPP)与胰岛素的mRNA和肽含量之比以及分泌量增加,这表明IAPP和胰岛素的表达受到不同的调节。因此,我们使用原位杂交和免疫细胞化学方法,研究了链脲佐菌素和四氧嘧啶糖尿病大鼠及小鼠中IAPP和胰岛素的胰岛表达情况。低剂量链脲佐菌素可使IAPP和胰岛素mRNA水平同等程度地降低至对照水平的约45%。相比之下,高剂量链脲佐菌素或四氧嘧啶使IAPP mRNA水平降低的幅度明显小于胰岛素mRNA(链脲佐菌素:24%对15%,P = 0.011;四氧嘧啶:15%对6%,P < 0.0001)。原位杂交和免疫细胞化学显示,实验性糖尿病中IAPP的表达主要发生在胰岛素细胞中。因此,在啮齿动物的实验性糖尿病中,IAPP和胰岛素基因表达受到不同调节,且IAPP主要在胰岛素细胞中表达。