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

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)737-747
Number of pages11
JournalActa Diabetologica
Issue number8
StatePublished - Aug 1 2017


  • Gastro-entero pancreatic factors
  • Human
  • Hypoglycemia
  • Islet

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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