Heterogeneity of proliferative markers in pancreatic β-cells of patients with severe hypoglycemia following Roux-en-Y gastric bypass.

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Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_B43F8666B75B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Heterogeneity of proliferative markers in pancreatic β-cells of patients with severe hypoglycemia following Roux-en-Y gastric bypass.
Périodique
Acta diabetologica
Auteur(s)
Patti M.E., Goldfine A.B., Hu J., Hoem D., Molven A., Goldsmith J., Schwesinger W.H., La Rosa S., Folli F., Kulkarni R.N.
ISSN
1432-5233 (Electronic)
ISSN-L
0940-5429
Statut éditorial
Publié
Date de publication
08/2017
Peer-reviewed
Oui
Volume
54
Numéro
8
Pages
737-747
Langue
anglais
Notes
Publication types: Journal Article ; Observational Study
Publication Status: ppublish
Résumé
Severe postprandial hypoglycemia with neuroglycopenia is an increasingly recognized, debilitating complication of Roux-en-Y gastric bypass (RYGB) surgery. Increased secretion of insulin and incretin hormones is implicated in its pathogenesis. Histopathologic examination of pancreas has demonstrated increased islet size and/or nuclear diameter in post-RYGB patients who underwent pancreatectomy for severe refractory hypoglycemia with neuroglycopenia (RYGB + NG). We aimed to determine whether β-cell proliferation or apoptosis is altered in RYGB + NG.
We performed an observational study to analyze markers of proliferation, apoptosis, cell cycle, and transcription factor expression in pancreatic tissue from affected RYGB + NG patients (n = 12), normoglycemic patients undergoing pancreatic surgery for benign lesions (controls, n = 6), and individuals with hypoglycemia due to insulinoma (n = 52).
Proliferative cell nuclear antigen (PCNA) expression was increased in insulin-positive cells in RYGB + NG patients (4.5-fold increase, p < 0.001 vs. controls) and correlated with β-cell mass. Ki-67 immunoreactivity was low in both RYGB + NG and controls, but did not differ between groups. Phospho-histone H3 levels did not differ between RYGB + NG and controls. PCNA and Ki-67 were both significantly lower in both controls and RYGB + NG than insulinomas. Markers of apoptosis and cell cycle (M30, p27, and p21) did not differ between groups. PDX1 and menin exhibited similar expression patterns, while FOXO1 appeared to be more cytosolic in RYGB + NG.
Markers of proliferation are heterogeneous in patients with severe post-RYGB hypoglycemia. Increased β-cell proliferation in some individuals may contribute to increased β-cell mass observed in severely affected patients.

Mots-clé
Adult, Aged, Blood Glucose/metabolism, Cell Proliferation, Female, Gastric Bypass/adverse effects, Gastric Inhibitory Polypeptide/metabolism, Humans, Hypoglycemia/etiology, Hypoglycemia/metabolism, Hypoglycemia/physiopathology, Incretins/metabolism, Insulin/secretion, Insulin-Secreting Cells/cytology, Insulin-Secreting Cells/metabolism, Male, Middle Aged, Pancreas/metabolism, Gastro-entero pancreatic factors, Human, Hypoglycemia, Islet
Pubmed
Web of science
Création de la notice
23/05/2017 14:48
Dernière modification de la notice
20/08/2019 15:22
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