Paulsson Johan F, Ludvigsson Johnny, Carlsson Annelie, Casas Rosaura, Forsander Gun, Ivarsson Sten A, Kockum Ingrid, Lernmark Åke, Marcus Claude, Lindblad Bengt, Westermark Gunilla T
Department of Clinical and Experimental Medicine, Division of Pediatrics and Diabetes Research Centre, Linköping University Hospital, Linköping, Sweden.
Department of Pediatrics, Lund University Hospital, Lund, Sweden.
PLoS One. 2014 Mar 26;9(3):e93053. doi: 10.1371/journal.pone.0093053. eCollection 2014.
AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP) is a beta cell hormone secreted together with insulin upon glucose stimulation. IAPP participates in normal glucose regulation, but IAPP is also known for its ability to misfold and form islet amyloid. Amyloid fibrils form through smaller cell toxic intermediates and deposited amyloid disrupts normal islet architecture. Even though IAPP and amyloid formation are much discussed in type 2 diabetes, our aim was to study the significance of IAPP in type 1 diabetes.
Plasma IAPP levels in children and adolescents with newly diagnosed type 1 diabetes (n = 224) were analysed and concentrations exceeding 100 pmol/L (127.2-888.7 pmol/L) were found in 11% (25/224). The IAPP increase did not correlate with C-peptide levels.
CONCLUSIONS/INTERPRETATION: Plasma levels of IAPP and insulin deviate in a subpopulation of young with newly-diagnosed type 1 diabetes. The determined elevated levels of IAPP might increase the risk for IAPP misfolding and formation of cell toxic amyloid in beta cells. This finding add IAPP-aggregation to the list over putative pathological factors causing type 1 diabetes.
目的/假设:胰岛淀粉样多肽(IAPP)是一种在葡萄糖刺激下与胰岛素一起分泌的β细胞激素。IAPP参与正常的葡萄糖调节,但IAPP也因其错误折叠并形成胰岛淀粉样物质的能力而闻名。淀粉样纤维通过较小的细胞毒性中间体形成,沉积的淀粉样物质会破坏正常的胰岛结构。尽管IAPP和淀粉样物质形成在2型糖尿病中被广泛讨论,但我们的目的是研究IAPP在1型糖尿病中的意义。
分析了新诊断的1型糖尿病儿童和青少年(n = 224)的血浆IAPP水平,发现11%(25/224)的患者浓度超过100 pmol/L(127.2 - 888.7 pmol/L)。IAPP的升高与C肽水平无关。
结论/解读:新诊断的1型糖尿病年轻患者亚群中,IAPP和胰岛素的血浆水平存在偏差。确定的IAPP升高水平可能会增加IAPP在β细胞中错误折叠和形成细胞毒性淀粉样物质的风险。这一发现将IAPP聚集添加到了导致1型糖尿病的假定病理因素列表中。