Tsuchiya Tami, Saisho Yoshifumi, Inaishi Jun, Sasaki Hironobu, Sato Midori, Nishikawa Masaru, Masugi Yohei, Yamada Taketo, Itoh Hiroshi
Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
Saisho Diabetes Clinic, Tokyo 164-0001, Japan.
Endocr J. 2022 Dec 28;69(12):1407-1414. doi: 10.1507/endocrj.EJ22-0170. Epub 2022 Aug 6.
The development of pancreatic cancer (PC) is associated with worsening of glucose tolerance. However, there is limited information about the effects of PC on islet morphology. The aim of this study was to elucidate changes in alpha and beta cell mass in patients with PC. We enrolled 30 autopsy cases with death due to PC (9 with diabetes; DM) and 31 age- and BMI-matched autopsy cases without PC (controls, 12 with DM). Tumor-free pancreatic sections were stained for insulin and glucagon, and fractional beta cell (BCA) and alpha cell area (ACA) were quantified. In addition, expression of de-differentiation markers, i.e., ALDH1A3 and UCN3, was qualitatively evaluated. The pancreas of subjects with PC showed atrophic and fibrotic changes. There was no significant difference in BCA in subjects with PC compared to controls (1.53 ± 1.26% vs. 0.95 ± 0.42%, p = 0.07). However, ACA and ACA to BCA ratio were significantly higher in subjects with PC compared to controls (2.48 ± 2.39% vs. 0.53 ± 0.26% and 1.94 ± 1.93 vs. 0.59 ± 0.26, respectively, both p < 0.001). Increased ACA to BCA ratio was observed in subjects with PC irrespective of the presence of DM. Qualitative evaluation of ALDH1A3 and UCN3 expression showed no significant difference between the groups. In conclusion, in subjects with PC, alpha to beta cell mass ratio is increased, which may contribute to the increased risk of worsening glucose metabolism. Further studies are warranted to elucidate the mechanisms of increased alpha to beta cell mass in patients with PC.
胰腺癌（PC）的发展与糖耐量恶化有关。然而，关于PC对胰岛形态影响的信息有限。本研究的目的是阐明PC患者α细胞和β细胞量的变化。我们纳入了30例因PC死亡的尸检病例（9例患有糖尿病；DM）和31例年龄及体重指数匹配的无PC尸检病例（对照组，12例患有DM）。对无肿瘤的胰腺切片进行胰岛素和胰高血糖素染色，并对β细胞分数（BCA）和α细胞面积（ACA）进行定量分析。此外，对去分化标志物即醛脱氢酶1A3（ALDH1A3）和尿皮质素3（UCN3）的表达进行定性评估。PC患者的胰腺呈现萎缩和纤维化改变。与对照组相比，PC患者的BCA无显著差异（1.53±1.26%对0.95±0.42%，p = 0.07）。然而，与对照组相比，PC患者的ACA以及ACA与BCA的比值显著更高（分别为2.48±2.39%对0.53±0.26%以及1.94±1.93对0.59±0.26，两者p均<0.001）。无论是否存在DM，PC患者均观察到ACA与BCA比值增加。对ALDH1A3和UCN3表达的定性评估显示两组之间无显著差异。总之，在PC患者中，α细胞与β细胞量的比值增加，这可能导致糖代谢恶化风险增加。有必要进一步开展研究以阐明PC患者α细胞与β细胞量增加的机制。
