Heterogeneity of Proliferative Markers in Pancreatic Beta Cells of Patients with Severe Hypoglycemia Following Roux-en-Y Gastric Bypass
Articolo
Data di Pubblicazione:
2017
Citazione:
Heterogeneity of Proliferative Markers in Pancreatic Beta Cells of Patients with Severe Hypoglycemia Following Roux-en-Y Gastric Bypass / M.E. Patti, A.B. Goldfine, J. Hu, D. Hoem, A. Molven, J. Goldsmith, W. Schwesinger, S.L. Rosa, F. Folli, R.N. Kulkarni. - In: ACTA DIABETOLOGICA. - ISSN 0940-5429. - 54:8(2017 Aug 30), pp. 737-747. [Epub ahead of print]
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 are 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 are altered in RYGB+NG.
Methods: We performed an observational study to analyze markers of proliferation, apoptosis, and 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. Phosphohistone
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
islet of Langerhans, proliferation, beta cells, ki67, PCNAislet, hypoglycemia, human, gastro-entero pancreatic factors
roux-en-Y gastric bypass (RYGB), neuroglycopenia (NG),GLP1
Elenco autori:
M.E. Patti, A.B. Goldfine, J. Hu, D. Hoem, A. Molven, J. Goldsmith, W. Schwesinger, S.L. Rosa, F. Folli, R.N. Kulkarni
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