Congenital Hyperinsulinism in Brazilian Neonates: A Study of Histology, KATP Channel Genes, and Proliferation of beta Cells

Autor(es)

Lovisolo, Silvana M. ^{[1, 2]} ; Mendonca, Berenice B. ^[3] ; Pinto, Emilia M. ^[1] ; Della Manna, Thais ^[4] ; Saldiva, Paulo Hilario N. ^[1] ; Zerbini, Maria Claudia N. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Univ Hosp, Anat Pathol Unit, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Clin Hosp, Endocrinol Unit, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Clin Hosp, Endocrinol Unit, Childrens Inst, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PEDIATRIC AND DEVELOPMENTAL PATHOLOGY; v. 13, n. 5, p. 375-384, SEP-OCT 2010.
• Citações Web of Science: 7

Resumo

Congenital hyperinsulinism (CHI) is a rare pancreatic beta-cell disease of neonates, characterized by inappropriate insulin secretion with severe persistent hypoglycemia, with regard to which many questions remain to be answered, despite the important acquisition of its molecular mechanisms in the last decade. The aim of this study was to examine pancreatic histology, beta-cell proliferation (immunohistochemistry with double staining for Ki-67/insulin), and beta-cell adenosine triphosphate-sensitive potassium channels genes from 11 Brazilian patients with severe medically unresponsive CHI who underwent pancreatectomy. Pancreatic histology and beta-cell proliferation in CHI patients were compared to pancreatic samples from 19 age-matched controls. Ten cases were classified as diffuse form (D-CHI) and 1 as focal form (F-CHI). beta-cell nucleomegaly and abundant cytoplasm were absent in controls and were observed only in D-CHI patients. The Ki-67 labeling index (Ki-67-LI) was used to differentiate the adenomatous areas of the F-CHI case (10.15%) from the ``loose cluster of islets'' found in 2 D-CHI samples (2.29% and 2.43%) and 1 control (1.54%) sample. The Ki-67-LI was higher in the F-CHI adenomatous areas, but D-CHI patients also had significantly greater Ki-67-LI (mean value = 2.41%) than age-matched controls (mean value = 1.87%) (P = 0.009). In this 1st genetic study of CHI patients in Brazil, no mutations or new polymorphisms were found in the 33-37 exons of the ABCC8 gene (SUR1) or in the entire exon of the KCNJ11 gene (Kir 6.2) in 4 of 4 patients evaluated. On the other hand, enhanced beta-cell proliferation seems to be a constant feature in CHI patients, both in diffuse and focal forms. (AU)

• Processo FAPESP: 08/56032-0 - Hiperinsulinismo congenito: estudo histopatologico, imuni-histoquimico e genetico-molecular envolvendo os canais ionicos de membrana k+/atp das celulas beta do pancreas
• Beneficiário: Maria Cláudia Nogueira Zerbini
• Modalidade de apoio: Auxílio à Pesquisa - Regular