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• W4381377504 abstract "Though Cyclin D2 (CCND2) has been considered to be essential for rodent beta cell proliferation, its expression in human beta cells is controversial. We reported CCND2 protein was abundantly expressed also in human perinatal beta cells at ADA 2019. This exclusive expression of CCND2 in the perinatal period would implicate a relationship with beta cell proliferation which is by far rare in human adults, while its regulation mechanism is unclear. GWAS studies identified rs76895963 in CCND2 locus as a genotype that reduced the susceptibility for type 2 diabetes by 50%. The SNP is also located in the sequence of CCND2-AS1, an anti-sense RNA. In this study, we explored the relationship between CCND2 and beta cell proliferation in humans, figuring out any possible regulations associated with CCND2-AS1. We obtained 49 pancreas samples from autopsies. Subjects were divided into 6 groups by age; fetus (F: gestational age 24 to 40 weeks), newborn (N: 0 days to1 month), infant (I: 2 to 12 months), toddler (T: 3 months to 4 years), child (C: 5 to 12 years), and adolescent (A: 13 to 19 years). Formalin-fixed paraffin-embedded sections were used for immunostaining and in situ hybridization analysis. Beta cell proliferation labeled with Ki67 was most abundant in N and rapidly decreased after T. Nuclear CCND2 expression was the highest in F followed by I and was almost not detected in C and A, showing a positive correlation with Ki67 though their peaks were different (p&lt;0.01). CCND2 mRNA was abundant in F and N but was also detectable in C and A. The correlation between CCND2 mRNA and protein was linear (p=0.0513). On the other hand, the expression of CCND2-AS1 was significantly correlated with CCND2 protein and Ki67 (p&lt;0.01 and &lt;0.05). Antisense RNAs are reported to show a variety of post-transcriptional regulations on their corresponding mRNA and protein. Our results suggest that CCND2-AS1 may positively regulate CCND2 expression and be a provisional therapeutic target for beta cell proliferation. Disclosure S.Osonoi: None. T.Sasaki: None. Y.Takeuchi: None. H.Mizukami: None." @default.
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• W4381377504 date "2023-06-20" @default.
• W4381377504 modified "2023-09-24" @default.
• W4381377504 title "1732-P: Correlation of Cyclin D2 with Cell Proliferation in Human Pancreatic Beta Cells and Possible Regulation by CCND2-AS1" @default.
• W4381377504 doi "https://doi.org/10.2337/db23-1732-p" @default.
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