Pancreatitis and pancreatic cancer in type 2 diabetes: underlying mechanisms and influence of diabetes medication
Final Report Abstract
During the time of my DFG research fellowship I had the opportunity to investigate the mechanisms underlying the increased risk of pancreatic cancer in type 2 diabetes (T2DM) and the influence of anti-diabetic drug treatment, namely the AMPK inhibitor metformin as well as the GLP-1 analogue exendin-4. While addressing the proposed aims it became clear that the pancreatic duct gland (PDG) compartment might represent a possible stem cell niche. This observation is highly relevant with regards to two aspects – tissue regeneration and repair. As PDGs harbor a minority of endocrine, insulin-positive cells, this compartment might serve as a new source for beta cells. Therefore, specifically targeting PDGs and directing the newly derived cells towards an endocrine lineage could be a novel approach to reverse the beta cell deficit in T2DM. Chronic stimulation of a stem cell pool as an attempt for tissue repair is associated with malignant transformations. The results provide further evidence that PDGs may represent a type of precursor for pancreatic cancer as they are expanded under conditions of chronic inflammation in T2DM. This expansion seems to be related to signals (chemokines) arising from apoptotic beta cells. Understanding the link between T2DM and pancreatic cancer is crucial for therapeutic intervention.
Publications
- Chronic GLP-1 receptor activation by Exendin-4 induces expansion of pancreatic duct glands and accelerates formation of dysplastic lesions and chronic pancreatitis in the G12D Kras mouse model. Diabetes, May;61 (5):1250-62, 2012
Gier B, Matveyenko AV, Kirakossian D, Dawson D, Dry SM, Butler PC
