Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL.
Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL.
Diabetes. 2020 Jan;69(1):60-66. doi: 10.2337/db19-0554. Epub 2019 Oct 9.
Within the human pancreas, exocrine and endocrine cells control secretion of digestive enzymes and production of hormones to maintain metabolic homeostasis, respectively. While the vast majority of type 1 diabetes research efforts have focused on endocrine function and autoimmunity, recent studies identified a series of unique features (e.g., reduced weight and volume, increased density of leukocytes) within the exocrine pancreas in this disease, but the mechanisms underlying these aberrancies are unknown. Therefore, we histologically assessed amylase, insulin, glucagon, lipase, and/or trypsinogen in 78 organ donor pancreata from birth through adulthood in control subjects and those at various stages of type 1 diabetes. While amylase-positive (AMY) acinar cells were detectable in pancreata from all study groups, tissues from individuals >2 years of age contained clusters of acinar cells devoid of amylase (AMY). A majority of these AMY cell clusters localized proximal to islets (i.e., peri-islet). Additionally, most AMY clusters were positive for the exocrine enzymes lipase and trypsinogen. Interestingly, type 1 diabetes pancreata displayed significant reductions in the frequency of these AMY cell clusters. These results support a contribution of the islet-acinar axis in pancreatic development and underscore a potential role for the exocrine pancreas in the pathogenesis of type 1 diabetes.
在人类胰腺中，外分泌细胞和内分泌细胞分别控制消化酶的分泌和激素的产生，以维持代谢平衡。虽然绝大多数 1 型糖尿病的研究都集中在外分泌功能和自身免疫上，但最近的研究在这种疾病中发现了一系列在外分泌胰腺中的独特特征（例如，体重和体积减少，白细胞密度增加），但这些异常的机制尚不清楚。因此，我们在对照组和各种 1 型糖尿病阶段的 78 例器官捐献者的胰腺中，从出生到成年，对淀粉酶、胰岛素、胰高血糖素、脂肪酶和/或胰蛋白酶原进行了组织学评估。虽然所有研究组的胰腺中都能检测到淀粉酶阳性（AMY）的腺泡细胞，但>2 岁个体的组织中存在无淀粉酶（AMY）的腺泡细胞簇。这些 AMY 细胞簇中的大多数位于胰岛附近（即胰岛周围）。此外，大多数 AMY 簇对胰脂肪酶和胰蛋白酶原呈阳性。有趣的是，1 型糖尿病的胰腺中这些 AMY 细胞簇的频率显著降低。这些结果支持胰岛-腺泡轴在胰腺发育中的作用，并强调了外分泌腺在 1 型糖尿病发病机制中的潜在作用。
