Professor Patrik Rorsman

Professor of Diabetic Medicine

Patrik Rorsman obtained his PhD at Uppsala University in 1986 and then worked for extended periods in the laboratory of Bert Sakmann (Nobel Prize 1991), where he learnt the patch-clamp technique, which has remained a work horse of his research ever since. After a brief period at Novo Nordisk in Denmark (1994-97), he became Professor of Physiology at Lund University.   He has been Professor of Diabetic Medicine at the University of Oxford since 2003.

He was awarded the Minkowski Prize (in 1996) and the Albert Renold Prize (2013) of the European Association for the Study of Diabetes and was elected Fellow of Royal Society (FRS) in 2014.

Research

Patrik Rorsman’s research focuses on insufficient insulin secretion combined with hypersecretion of glucagon result in the metabolic dysregulation linked with clinical diabetes.

He has published more than 220 papers dealing with the function of the pancreatic islet cells and has performed pioneering studies on the cellular and molecular regulation of pancreatic islet hormone secretion, the mechanisms that underlie the ability of the different types of islet cell to sense changes in the body’s metabolic state and adjust the release of insulin and glucagon to the functional requirements.

His research aims to explain the fundamental mechanisms regulating insulin and glucagon secretion. The work involves a combination of techniques to study secretion at the molecular, cellular and systemic levels. This requires sophisticated methodology to record the minute electrical currents flowing across biological membranes and secretion in individual cells at millisecond resolution. Optical techniques that allow monitoring the movements of single secretory granules within the cell prior and during secretion are also used. This work has led to an improved understanding of the normal regulation of insulin and glucagon secretion. This provides a knowledge base needed to define the defects associated with diabetes and for the development of novel therapeutic interventions.

His most recent work focuses on the mechanisms by which weight reduction surgery leads to rapid resolution of diabetes. These studies have highlighted an important role of the gut peptide PYY as the mediator of the effects. It is hoped that these observations ultimately can be translated into a non-surgical treatment of type-2 diabetes.

Publications

Ramracheya RD, McCulloch LJ, Clark A, Wiggins D, Johannessen H, Olsen MK, Cai X, Zhao CM, Chen D, Rorsman P. 2016. PYY-dependent restoration of impaired insulin and glucagon secretion in type 2 diabetes following Roux-En-Y gastric bypass surgery. Cell Rep. pii: S2211-1247(16)30397-7.

Shigeto M, Ramracheya R, Tarasov AI, Cha CY, Chibalina MV, Hastoy B, Philippaert K, Reinbothe T, Rorsman N, Salehi A, Sones WR, Vergari E, Weston C, Gorelik J, Katsura M, Nikolaev VO, Vennekens R, Zaccolo M, Galione A, Johnson PR, Kaku K, Ladds G, Rorsman P. 2015. GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation. J Clin Invest. 125:4714-28.

Zhang Q, Ramracheya R, Lahmann C, Tarasov A, Bengtsson M, Braha O, Braun M, Brereton M, Rorsman P. 2013. Role of KATP channels in glucose-regulated glucagon secretion and impaired counterregulation in type 2 diabetes. Cell Metab, 18 (6), pp. 871-882.

Rorsman P, Braun M. 2013. Regulation of insulin secretion in human pancreatic islets. Annu Rev Physiol, 75 (1), pp. 155-179.

Rosengren AH, Braun M, Mahdi T, Andersson SA, Travers ME, Shigeto M, Zhang E, Almgren P et al (2012). Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes. Diabetes, 61 (7), pp. 1726-1733.

De Marinis YZ, Salehi A, Ward CE, Zhang Q, Abdulkader F, Bengtsson M, Braha O, Braun M et al (2010). GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis. Cell Metab, 11 (6), pp. 543-553.

Hoppa MB, Collins S, Ramracheya R, Hodson L, Amisten S, Zhang Q, Johnson P, Ashcroft FM, Rorsman P. (2009). Chronic palmitate exposure inhibits insulin secretion by dissociation of Ca(2+) channels from secretory granules. Cell Metab, 10 (6), pp. 455-465.

Braun M, Ramracheya R, Bengtsson M, Zhang Q, Karanauskaite J, Partridge C, Johnson PR, Rorsman P. 2008. Voltage-gated ion channels in human pancreatic beta-cells: electrophysiological characterization and role in insulin secretion. Diabetes, 57 (6), pp. 1618-1628.

MacDonald PE, De Marinis YZ, Ramracheya R, Salehi A, Ma X, Johnson PR, Cox R, Eliasson L, Rorsman P. (2007). A K ATP channel-dependent pathway within alpha cells regulates glucagon release from both rodent and human islets of Langerhans. PLoS Biol, 5 (6), pp. e143.

Zhang Q, Bengtsson M, Partridge C, Salehi A, Braun M, Cox R, Eliasson L, Johnson PR et al (2007). R-type Ca(2+)-channel-evoked CICR regulates glucose-induced somatostatin secretion. Nat Cell Biol, 9 (4), pp. 453-460.

MacDonald PE, Braun M, Galvanovskis J, Rorsman P. 2006. Release of small transmitters through kiss-and-run fusion pores in rat pancreatic beta cells. Cell Metab, 4 (4), pp. 283-290.

Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M. 2004. A pancreatic islet-specific microRNA regulates insulin secretion. Nature, 432 (7014), pp. 226-230.

Schulla V, Renström E, Feil R, Feil S, Franklin I, Gjinovci A, Jing XJ, Laux D et al (2003). Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice. EMBO J, 22 (15), pp. 3844-3854.

Ammälä C, Ashcroft FM, Rorsman P. 1993. Calcium-independent potentiation of insulin release by cyclic AMP in single beta-cells. Nature, 363 (6427), pp. 356-358.