Review article: pancreatic renin–angiotensin systems in health and disease J. R. A. Skipworth* ,  , G. Szabadkai à , S. W. M. Olde Damink* , ,– , P. S. Leung**, S. E. Humphries    & H. E. Montgomery àà *Department of Surgery and Interven- tional Science, UCL, London, UK.   Department of Hepatopancreaticobil- iary Surgery, Royal Free Hospital, London, UK. à Department of Cell and Develop- mental Biology, UCL, London, UK. – Department of Surgery, Maastricht University Medical Centre, Maastricht, Netherlands. **School of Biomedical Sciences, Faculty of Medicine, Chinese Univer- sity of Hong Kong, Hong Kong, China.    Centre for Cardiovascular Genetics & UCL Genetics Institute, UCL, London, UK. àà Institute of Human Health and Performance, UCL, London, UK. Correspondence to: Mr J. R. A. Skipworth, UCL Division of Surgical and Interventional Sciences, 4th Floor, Medical School Building, 74 Huntley Street, University College London, London, WC1E 6AU, UK. E-mail: j.skipworth@ucl.ac.uk Publication data Submitted 31 August 2010 First decision 30 September 2010 Resubmitted 22 July 2011 Accepted 24 July 2011 EV Pub Online 19 August 2011 This uncommissioned review article was subject to full peer-review. SUMMARY Background In addition to the circulating (endocrine) renin–angiotensin system (RAS), local renin–angiotensin systems are now known to exist in diverse cells and tissues. Amongst these, pancreatic renin–angiotensin systems have recently been identified and may play roles in the physiological regulation of pan- creatic function, as well as being implicated in the pathogenesis of pancre- atic diseases including diabetes, pancreatitis and pancreatic cancer. Aim To review and summarise current knowledge of pancreatic renin–angioten- sin systems. Methods We performed an extensive PubMed, Medline and online review of all rele- vant literature. Results Pancreatic RAS appear to play various roles in the regulation of pancreatic physiology and pathophysiology. Ang II may play a role in the develop- ment of pancreatic ductal adenocarcinoma, via stimulation of angiogenesis and prevention of chemotherapy toxicity, as well as in the initiation and propagation of acute pancreatitis (AP); whereas, RAS antagonism is capable of preventing new-onset diabetes and improving glycaemic control in dia- betic patients. Current evidence for the roles of pancreatic RAS is largely based upon cell and animal models, whilst definitive evidence from human studies remains lacking. Conclusions The therapeutic potential for RAS antagonism, using cheap and widely available agents, and may be untapped and such roles are worthy of active investigation in diverse pancreatic disease states. Aliment Pharmacol Ther 2011; 34: 840–852 840 ª 2011 Blackwell Publishing Ltd doi:10.1111/j.1365-2036.2011.04810.x Alimentary Pharmacology and Therapeutics