Abstract
Background: The incidence of pancreatic cancer is increasing year-by-year in Japan. Among the diseases that complicate pancreatic cancer, diabetes is the most common. Recently, it has become evident that patients suffering from diabetes and obesity show increased expression of osteopontin (OPN). The purpose of this study was to investigate the effect of high glucose and high insulin culture conditions on a human pancreatic duct epithelial cell line (HPDE-6), focusing particularly on OPN expression. Methods: HPDE-6 were cultured under various conditions, employing several combinations of glucose (normal, 6 mM high, 30 mM, and 60 mM) and insulin (0.1 nM, 1 nM) concentration. Results: HPDE-6 cell proliferation was significantly accelerated under high glucose culture conditions in comparison to samples in 6 mM glucose, and was more prominent under high insulin conditions. At the same time, the expression of OPN mRNA was also increased significantly. In comparison with 6 mM glucose, the expression of 8-OHdG DNA was increased in high glucose culture. Conclusion: HPDE-6 cells show accelerated proliferation and increased OPN expression when cultured under high glucose and high insulin conditions. Furthermore, the cells show increased oxidative stress in the presence of high glucose.
Highlights
In clinical practice, it is known that many cases of pancreatic cancer become evident when patients are investigated for a worsening in glycemic control
Detection of pancreatic cancer is necessary for an improved prognosis, and delineation of patients who are at high risk is a major issue
Clarifying the pathophysiology of diabetes in the pancreatic duct epithelium is believed to be very important for achieving the goal of early detection of pancreatic cancer
Summary
It is known that many cases of pancreatic cancer become evident when patients are investigated for a worsening in glycemic control. 2017, 18, 807 relative risk of pancreatic cancer in patients with diabetes was 2.1 (95% CI: 1.1–2.7) [5]. It has become evident that patients suffering from diabetes and obesity show increased expression of osteopontin (OPN). The purpose of this study was to investigate the effect of high glucose and high insulin culture conditions on a human pancreatic duct epithelial cell line (HPDE-6), focusing on OPN expression. Results: HPDE-6 cell proliferation was significantly accelerated under high glucose culture conditions in comparison to samples in 6 mM glucose, and was more prominent under high insulin conditions. Conclusion: HPDE-6 cells show accelerated proliferation and increased OPN expression when cultured under high glucose and high insulin conditions. The cells show increased oxidative stress in the presence of high glucose
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