Molecular studies of diabetes and pancreatic exocrine dysfunction

The number of diabetic people in the world is increasing rapidly and the term diabetes epidemic is being applied to describe the phenomenon. Some aspects of the disease mechanisms are known, but there is an urgent need for more insight which can facilitat e the development of treatment that addresses the disease mechanisms. By studying patients in families with a clustering of type 1 and type 2 diabetes, we recently identified a novel syndrome of diabetes combined with pancreatic exocrine dysfunction (i.e. defective secretion of enzymes needed for the digestion of food) with a new genetic cause (Carboxyl-ester lipase gen mutations), the MODY8 syndrome (maturity-onset diabetes of the young type 8). These findings were presented in the leading genetic journ al Nature Genetics with an accompanying editorial. Since around 20% of type 1 and type 2 diabetes patients have signs of pancreatic exocrine dysfunction, we were amazed to find that other genetic variants in the involved gene were clearly more prevalent a lso in type 1 and type 2 diabetes patients with pancreatic exocrine dysfunction. The disease mechanism (how the genetic variants lead to diabetes) is poorly known, and subsequently it is difficult to target therapy that addresses the disease mechanism. He nce, we have an established and ongoing collaboration with C. Ronald Kahn and Rohit Kulkarni who are world-leading scientists within the field of diabetes and cellular physiology at Joslin Diabetes Center, Harvard Medical School, in an attempt to solve th e puzzle. We have collaborated on the studies of cell and animal models since 2004 and have already some insight into the disease mechanism. We now aim to further pursue the studies of the disease mechanism of MODY8, based on cellular models and animal mo dels.