Pancreatitis and pancreatic cancer in type 2 diabetes: underlying mechanisms and influence of diabetes medication

• Applicant: Dr. Belinda Gier
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2011 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 194957746

The major aim of the study is to identify signals and molecular mechanisms linking diabetes to an increased risk of pancreatitis and pancreatic cancer, emphasizing possible influences of anti-diabetic drug treatment.Type 2 diabetes is a common metabolic disorder characterized by insulin resistance and impaired insulin secretion. Obesity and type 2 diabetes are both associated with an increased risk of chronic pancreatitis, which is the most important risk factor for pancreatic cancer. Pancreatic cancer is characterized by clinically rapid onset, resistance to treatment and poor outcome. There is an increasing appreciation that the choice of anti-diabetic therapy may influence the risk for pancreatitis or pancreatic cancer. In this respect, concern has been raised about a novel drug class, glucagon-like peptide-1 mimetic drugs. In contrast, metformin, which is an oral anti-diabetic drug that has been used for more than 50 years, is protective against both pancreatitis and pancreatic cancer in humans. Both chronic pancreatitis and pancreatic cancer are believed to originate from pancreatic duct cells, and more recently from the pancreatic duct gland compartment related to pancreatic ducts. We hypothesize that diabetes and obesity increase the risk for pancreatitis and pancreatic cancer through signals that induce increased pancreatic duct and duct gland cell turnover. Moreover, we hypothesize that GLP-1 activation amplifies this risk by acting on proliferation pathways while metformin attenuates it by showing opposite effects on duct cell proliferation. In this application, we propose studies to test these hypotheses as well as to establish the signals that regulate pancreatic duct and duct gland cell turnover in this environment.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Peter C. Butler