Abstract：
Histopathological heterogeneity in the human pancreas is well documented; however, functional evidence at the tissue level is scarce. Herein, we investigate in situ glucose-stimulated islet and carbachol-stimulated acinar cell secretion across the pancreas head (PH), body (PB), and tail (PT) regions in donors without diabetes (ND; n = 15), positive for one islet autoantibody (1AAb+; n = 7), and with type 1 diabetes (T1D; <14 months duration, n = 5). Insulin, glucagon, pancreatic amylase, lipase, and trypsinogen secretion along with 3D tissue morphometrical features are comparable across regions in ND. In T1D, insulin secretion and beta-cell volume are significantly reduced within all regions, while glucagon and enzymes are unaltered. Beta-cell volume is lower despite normal insulin secretion in 1AAb+, resulting in increased volume-adjusted insulin secretion versus ND. Islet and acinar cell secretion in 1AAb+ are consistent across the PH, PB, and PT. This study supports low inter-regional variation in pancreas slice function and, potentially, increased metabolic demand in 1AAb+.
摘要：
人类胰腺的组织病理学异质性是有据可查的；然而，组织水平的功能证据很少。在这里，我们研究了通过胰头（PH）的原位葡萄糖刺激的胰岛和卡巴胆碱刺激的腺泡细胞分泌，主体(PB),和没有糖尿病的供体的尾部（PT）区域（ND；n=15），一种胰岛自身抗体阳性（1AAb+；n=7），和1型糖尿病（T1D；病程<14个月，n=5)。胰岛素,胰高血糖素,胰淀粉酶,脂肪酶,胰蛋白酶原分泌以及3D组织形态测量特征在ND的各个区域中具有可比性。在T1D中,所有区域的胰岛素分泌和β细胞体积都显著减少，而胰高血糖素和酶没有改变。β细胞体积较低，尽管1AAb+的胰岛素分泌正常，导致与ND相比，体积调节的胰岛素分泌增加。1AAb+中的胰岛和腺泡细胞分泌在整个PH中是一致的，PB,和PT。这项研究支持胰腺切片功能的低区域间变异，潜在的,1AAb+的代谢需求增加。
