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.

中文翻译：

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对照、自身抗体阳性和 1 型糖尿病胰腺组织中淀粉酶表达的时间分析

在人胰腺内，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稳态。虽然绝大多数 1 型糖尿病研究工作都集中在内分泌功能和自身免疫上，但最近的研究发现了这种疾病的外分泌胰腺内的一系列独特特征（例如，重量和体积减少，白细胞密度增加），但机制这些异常背后的原因是未知的。因此，我们通过组织学评估了 78 名器官供体胰腺从出生到成年的对照受试者和处于 1 型糖尿病不同阶段的受试者的淀粉酶、胰岛素、胰高血糖素、脂肪酶和/或胰蛋白酶原。虽然在所有研究组的胰腺中均可检测到淀粉酶阳性 (AMY+) 腺泡细胞，但个体组织 > 2 岁年龄组包含无淀粉酶 (AMY-) 的腺泡细胞簇。大多数这些 AMY- 细胞簇位于胰岛的近端（即，胰岛周围）。此外，大多数 AMY- 簇对外分泌酶脂肪酶和胰蛋白酶原呈阳性。有趣的是，1 型糖尿病胰腺显示这些 AMY- 细胞簇的频率显着降低。这些结果支持胰岛-腺泡轴在胰腺发育中的作用，并强调了外分泌胰腺在 1 型糖尿病发病机制中的潜在作用。1 型糖尿病胰腺显示这些 AMY- 细胞簇的频率显着降低。这些结果支持胰岛-腺泡轴在胰腺发育中的作用，并强调了外分泌胰腺在 1 型糖尿病发病机制中的潜在作用。1 型糖尿病胰腺显示这些 AMY- 细胞簇的频率显着降低。这些结果支持胰岛-腺泡轴在胰腺发育中的作用，并强调了外分泌胰腺在 1 型糖尿病发病机制中的潜在作用。