4.2 Article

Increased alpha cell to beta cell ratio in patients with pancreatic cancer

Journal

ENDOCRINE JOURNAL
Volume -, Issue -, Pages -

Publisher

JAPAN ENDOCRINE SOC
DOI: 10.1507/endocrj.EJ22-0170

Keywords

Beta cell mass; Alpha cell mass; Pancreatic cancer

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology [20K17542, 21K08535]

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The alpha to beta cell mass ratio is increased in patients with pancreatic cancer, which may contribute to worsened glucose metabolism. Further studies are needed to elucidate the mechanisms behind the increased alpha to beta cell mass in these patients.
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, bothp < 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.

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