Grant: Operating Grant

Acute pancreatitis (AP) causes a great deal of acute and chronic morbidity and mortality, and at considerable financial costs to health care in Canada. The most common cause of AP is alcohol, affecting 10% of alcoholics. There is still no effective specific treatment directed at the pathogenesis of alcoholic AP because the postulated disease mechanisms could not be directly tested on human pancreatic tissue. Glucagon-like peptide 1 (GLP-1)-based therapies, which potentiate glucose-mediated insulin secretion, is the new panacea and most promising treatment for diabetes, and is a multi-billion dollar pharmaceutical market. However, these drug treatments have been shown to exhibit a six-fold increase in AP, the basis of this dangerous side effect is totally unknown. To effectively address these two conditions, we were first to develop the rodent and human models of preparing fresh pancreatic slices to genuinely examine normal pancreatic exocrine cell biology and disease mechanisms. Our goals are to: 1) Determine the cellular basis of human alcoholic AP; and 2) Determine the cellular basis of human AP caused by GLP-1 drug treatment for diabetes. This work will elucidate clinically relevant insights underlying human alcoholic and GLP-1-induced AP, which will identify novel treatments for alcoholic AP and impact current diabetes management in patients taking GLP-1 drugs.