Atypical Forms of Congenital Hyperinsulinism in Infancy Are Associated With Mosaic Patterns of Immature Islet Cells

作者：Han, Bing; Mohamed, Zainab; Estebanez, Maria Salomon; Craigie, Ross J.; Newbould, Melanie; Cheesman, Edmund; Padidela, Raja; Skae, Mars; Johnson, Matthew; Flanagan, Sarah; Ellard, Sian; Cosgrove, Karen E.; Banerjee, Indraneel; Dunne, Mark J.^*

来源：Journal of Clinical Endocrinology & Metabolism, 2017, 102(9): 3261-3267.

DOI：10.1210/jc.2017-00158

• HUMAN PANCREAS
• BETA-CELLS
• HYPOGLYCEMIA
• MUTATION
• PROLIFERATION
• MANAGEMENT
• PHENOTYPE
• DIAGNOSIS
• CHILDREN
• SUBSET

Objectives: We aimed to characterize mosaic populations of pancreatic islet cells from patients with atypical congenital hyperinsulinism in infancy (CHI-A) and the expression profile of NKX2.2, a key transcription factor expressed in beta-cells but suppressed in delta-cells in the mature pancreas. @@@ Patients/Methods: Tissue was isolated from three patients with CHI-A following subtotal pancreatectomy. CHI-A was diagnosed on the basis of islet mosaicism and the absence of histopathological hallmarks of focal and diffuse CHI (CHI-D). Immunohistochemistry was used to identify and quantify the proportions of insulin-secreting beta-cells and somatostatin-secreting delta-cells in atypical islets, and results were compared with CHI-D (n = 3) and age-matched control tissues (n = 3). @@@ Results: In CHI-A tissue, islets had a heterogeneous profile. In resting/quiescent islets, identified by a condensed cytoplasm and nuclear crowding, beta-cells were reduced to <50% of the total cell numbers in n = 65/70 islets, whereas delta-cell numbers were increased with 85% of islets (n = 49/57) containing >20% delta-cells. In comparison, all islets in control tissue (n = 72) and 99% of CHI-D islets (n = 72) were composed of <50% beta-cells, and >20% delta-cells were found only in 12% of CHI-D (n = 8/66) and 5% of control islets (n = 3/60). Active islets in CHI-A tissue contained proportions of beta-cells and delta-cells similar to those of control and CHI-D islets. Finally, when compared with active islets, quiescent islets had a twofold higher prevalence of somatostatin/NKX2.2(+) coexpressed cells. @@@ Conclusions: Marked increases in NKX2.2 expression combined with increased numbers of delta-cells strongly imply that an immature delta-cell profile contributed to the pathobiology of CHI-A.

• 出版日期2017-9