BSPED2015 Poster Presentations (1) (7 abstracts)
Islet cell proliferation is inappropriately maintained in the pancreas of children with congenital hyperinsulinism in infancy
Bing Han 1 , Melanie Newbould 2 , Edmund Cheesman 2 , Gauri Batra 2 , Ross Craigie 2 , Zainab Mohamed 1 , Lindsey Rigby 2 , Raja Padidela 2 , Mars Skae 2 , Karen Cosgrove 1 , Mark Dunne 1 & Indraneel Banerjee 2
1University of Manchester, Manchester, UK; 2Royal Children’s Hospital, Manchester, UK.
Background: In diffuse CHI (CHI-D) insulin release is uncontrolled due to mutations in the ABCC8/KCNJ11 genes. Increased rates of cell proliferation have also been reported, but the mechanisms responsible for this are unknown. We hypothesized that this may arise as a consequence of failure to terminate proliferation in the neonatal period. Here, we examined the proliferative index (PI) of islet cells in CHI-D patients and compared this with focal CHI (CHI-F) which is caused by loss of cell cycle repression in β-cells within the focal domain.
Methods: PI was assessed by Ki67 expression using tissue from CHI patients positive for mutations in the ABCC8 gene - CHI-D (n=10), CHI-F (n=6), and neonatal (n=12), juvenile and adult control tissues (n=5). Analysis of digitized images was used to calculate the average PI (mean ± S.E.M).
Results: In CHI tissue – including the non-lesion domains of CHI-F, we found an inverse correlation between PI with age, but the rates of decline were markedly decreased when compared to control tissues. Thus, up to 8 weeks following birth 8±0.4% (n=5) of cells were Ki67+; 4±0.4% (n=3) up to 7 months and 3% up to 10 months of age. Importantly, whilst there was an increase in Ki67+cells within focal lesions (due to defects in p57kip2), there was little overall difference in the PI between the non-lesion domains of CHI-F and CHI-D; 4±0.4 vs. 5±1, respectively.
Summary/conclusion: In control and CHI tissues, we found an inverse correlation between the PI of the exocrine and endocrine pancreas and age. We suggest that enhanced rates of proliferation in CHI islet cells arise from failure to terminate proliferation by a mechanism that is not directly attributable to the genetic cause of disease.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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