Expression of connexin26 in islets of Langerhans is associated with impaired glucose tolerance in patients with pancreatic adenocarcinoma

Pancreas. 2004 Nov;29(4):284-90. doi: 10.1097/00006676-200411000-00007.

Abstract

Objectives: Impairment of glucose tolerance is one of the leading clinical presentations in patients with pancreatic carcinoma. The mechanism of disturbed glucose metabolism, however, is still under debate. Using microarray technology, key mechanisms of deregulated molecular functions of cancer cell-specific mRNAs and tumor-induced mRNAs in peritumorous tissue should be identified in pancreatic ductal adenocarcinoma (PDAC) by comparison to chronic pancreatitis and normal pancreas.

Methods: Forty-three mRNAs were abundant in tissue specimens of patients operated due to pancreatic carcinoma but absent or of low abundance in chronic pancreatitis and normal pancreas. One of these mRNAs encodes the gap junction protein connexin26, known as a tumor suppressor, which was 10.8- and 6.9-fold more abundant in pancreatic carcinoma than in normal pancreas and chronic pancreatitis, respectively. Quantitative RT-PCR was performed for connexin26, with mRNA being expressed 26.7- and 2.9-fold more than in normal pancreas (n = 6), in pancreatic carcinoma (n = 7), and chronic pancreatitis (n = 8), respectively.

Results: By immunohistochemistry, connexin26 was predominantly localized to the islets in the vicinity of the pancreatic carcinoma tissue. Control sections of tissue with chronic pancreatitis and normal pancreas show connexin26 expression in the islets as well. Interestingly, the level of mRNA abundance (fold over normal pancreas) in RT-PCR correlates (r = 0.62) with the 2h value of the pre-operative oral glucose tolerance test of these patients.

Conclusion: Whether overexpressed connexin26 in pancreatic cancer is a cause of impaired glucose tolerance remains to be elucidated in further experimental studies.

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / genetics*
  • Connexin 26
  • Connexins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glucose Intolerance / genetics*
  • Glucose Metabolism Disorders / etiology
  • Glucose Metabolism Disorders / genetics*
  • Humans
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / complications
  • Pancreatic Neoplasms / genetics*

Substances

  • Connexins
  • GJB2 protein, human
  • Connexin 26