Abstract:

Insulin resistance is closely associated with obesity on one hand, and with a raft of major diseases on the other, including diabetes, fatty liver disease, cancer and subfertility. However “insulin resistance” means different things to different investigators. To the clinician or physiologist, it means attenuated glucose-lowering ability of systemic insulin, while to a cell signaller it implies a shift in a dose response curve of insulin with respect to one or more insulin-triggered cellular processes. In this talk, some lessons learned from 30 years of genetic studies of human severe insulin resistance – and associated disease modelling - will be summarised, emphasising that pandemic insulin resistance is much more than a cellular insulin signalling defect. How agnostic genetic studies have implicated cellular processes as diverse as DNA replication, mitochondrial fusion, and centrosomal dynamics in insulin resistance, and the rage of new questions arising, will be discussed.

Bio:

Robert Semple is Professor of Translational Molecular Medicine, and a Dean of Postgraduate Research at the University of Edinburgh, UK. He trained in Biochemistry and then Medicine at the University of Cambridge, with clinical postgraduate training in London and Cambridge, including a PhD in the laboratory of Prof. Sir Stephen O’Rahilly. Over the past 15 years his clinical and research interests have centred on acquired and monogenic disorders of insulin signalling, growth and lipodystrophy. He aims to use rare human conditions to improve understanding of the cell and molecular basis of pandemic “insulin resistance”, and of the mechanisms linking it to major disease, and on translating research findings into clinical benefits for patients. A key focus is on using human genetics to gain insights into determinants of adipose resilience across the lifespan.