20 février 2025: Pr Patrik Rorsman

12H30
CMU - AUDITOIRE Müller (A250)

suivi d'un apéritif

Hôte: Pr Pedro HERRERA
Centre facultaire du diabète &
Département de  médecine génétique et développement, Faculté de médecine UNIGE

Pr Patrik rorsman

FRS FMedSci
Professor of Diabetic Medicine
Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM),
Radcliffe Department of Medicine, University of Oxford

« The glucagon-secreting alpha-cell: from the clinic to the laboratory bench and back to bedside »

The plasma glucose concentration is maintained by a continuous tug of war between the actions of insulin (lowering) and glucagon (increasing) that are secreted by the beta- and alpha-cells of the pancreatic islets, respectively. Diabetes is caused by a lack of insulin, the impact of which is exacerbated by defects of glucagon secretion. Diabetes research has traditionally had a “beta-centric” perspective but recently there has been renewed interest in glucagon and the alpha-cells and diabetes is now often referred to as a “bihormonal disorder”. In his lecture, Pr Rorsman will discuss the complex crosstalk between the islet cells in the healthy state and how it becomes disrupted in diabetes. In particular, he will consider the failure of the alpha-cells to release enough glucagon at low glucose, which leads to an increased risk of the blood glucose concentration falling to dangerously low (even fatal) levels; some estimates suggest that this is the cause of 10% of the deaths in insulin-treated patients. Pr Rorsman will describe data gleaned from studies on mouse models of diabetes as well as human islets from donors with diabetes. Finally, he will turn to the question of whether physiologically appropriate regulation of glucagon can be restored by repurposing of drugs already used in diabetes therapy.


Biography

Pr Patrik Rorsman has worked in experimental diabetes research since 1980. His work has focused on the regulation of pancreatic hormone secretion, which his group studied by a combination of biochemical, molecular biological, biophysical and optical approaches. This research encompasses studies not only of the insulin-producing beta-cells but also the glucagon-secreting alpha-cells and the somatostatin-releasing delta-cells. This work has unveiled the complexity of the cross-talk between the different islet cells.   
Three important achievements include: (i) the elucidation of how glucose regulates pancreatic hormone secretion via changes in electrical activity; (ii) the modulation of hormone release by metabolites, hormone and pharmacological agents using techniques that allow secretion to be studied with millisecond resolution and down to individual molecules; and (iii) the development of techniques that allow high-quality electrophysiological measurements in intact pancreatic islets.   
A particular strength of Pr Rorsman's research has been the opportunity to extend the experimental studies to human pancreatic islets and this work has revealed that there are major and important differences between human islet cells and their rodent counterparts. Currently, much of his work is devoted to the understanding of how islet hormone release becomes disrupted in diabetes with a view to formulating novel therapeutic strategies. His group is particularly interested in hypoglycemia, which has previously not attracted so much interest among experimentalists. Hypoglycemia is of course a major problem in insulin-treated patients and we are therefore looking into the possibility of restoring alpha-cell function in type 1 diabetic patients.

14 janv. 2025

Frontiers in biomedicine