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Acta Diabetologica
Published in: Acta Diabetologica 8/2017

01-08-2017 | Original Article

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

Authors: Mary-Elizabeth Patti, Allison B. Goldfine, Jiang Hu, Dag Hoem, Anders Molven, Jeffrey Goldsmith, Wayne H. Schwesinger, Stefano La Rosa, Franco Folli, Rohit N. Kulkarni

Published in: Acta Diabetologica | Issue 8/2017

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Abstract

Aims

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.

Methods

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).

Results

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.

Conclusions

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.
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Metadata
Title
Heterogeneity of proliferative markers in pancreatic β-cells of patients with severe hypoglycemia following Roux-en-Y gastric bypass
Authors
Mary-Elizabeth Patti
Allison B. Goldfine
Jiang Hu
Dag Hoem
Anders Molven
Jeffrey Goldsmith
Wayne H. Schwesinger
Stefano La Rosa
Franco Folli
Rohit N. Kulkarni
Publication date
01-08-2017
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 8/2017
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-017-1001-2

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