Enhanced proliferation in colorectal epithelium of patients with type 2 diabetes correlates with β-catenin accumulation

J Diabetes Complications. 2014 Sep-Oct;28(5):689-97. doi: 10.1016/j.jdiacomp.2014.05.001. Epub 2014 May 15.

Abstract

Aims: β-Catenin accumulation promotes proliferation. However, the correlation between proliferation of colorectal epithelium and β-catenin in type 2 diabetes mellitus (DM) patients remains unclear.

Methods: Colorectal epithelium samples from distal ends of colorectal adenocarcinomas without histological aberrances were divided into two groups: DM patients with type 2 DM for more than 1year (n=27) and non-DM patients without hyperglycemia (n=20). Samples from patients without colorectal epithelial disease or hyperglycemia served as a control group (n=6). Proliferative index was calculated as the percentage of proliferating cell nuclear antigen positive cells. Wnt/β-catenin signaling was assessed immunohistochemically and phosphorylation of β-catenin was assessed by immunofluorescence.

Results: Compared with the non-DM or control group, the proliferative index and expression of lactate dehydrogenase A and Wnt/β-catenin signaling were significantly higher in the DM group (all p<0.01). The proliferative index correlated positively with β-catenin expression (Spearman correlation coefficient=0.55; p<0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of β-catenin were detected in the DM group (all p<0.01).

Conclusions: Enhanced proliferation, accompanied by increased aerobic glycolysis, was detected in colorectal epithelium of patients with diabetes. β-Catenin accumulation with altered phosphorylation correlated with the proliferative changes.

Keywords: Colorectal epithelium; Diabetes; Phosphorylation; Proliferation; β-Catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma* / complications
  • Adenoma* / metabolism
  • Adenoma* / pathology
  • Adult
  • Aged
  • Case-Control Studies
  • Cell Proliferation*
  • Colorectal Neoplasms* / complications
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / metabolism
  • Diabetes Mellitus, Type 2* / pathology
  • Female
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology*
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Lactate Dehydrogenase 5
  • Male
  • Middle Aged
  • Proliferating Cell Nuclear Antigen / metabolism
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • Isoenzymes
  • Proliferating Cell Nuclear Antigen
  • beta Catenin
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5