Human Genetic Disorders of Insulin Action Image Prof Robert Semple, Chair of Translational Molecular Medicine, CMVM Dean of Postgraduate Research Research in a Nutshell Reduced ability of insulin to lower blood glucose is known as insulin resistance. This is common, is closely associated with obesity, and is believed to drive numerous major diseases. We aim to understand how it occurs and how it is linked to diabetes, fatty liver, high blood fat levels, reduced fertility and cancer. To do this we focus on rare and severe disorders caused by changes in individual genes, including severe insulin resistance, low blood glucose, and/or excess tissue growth. We study people with known genetic changes, look for new genetic changes in studies of people and populations, and investigate the changes we find in mice and cells. Specific interests include:Defects of insulin signalling: We use these to test which diseases are caused by lack of insulin action, and which by compensatory increased insulin action. We are systematically studying all possible insulin receptor mutations, and are investigating anti-receptor antibodies as potential treatments for extreme insulin receptor defects.Mutations increasing insulin-like signalling: Activating mutations, especially in the PIK3CA gene, usually occur after conception, are found patchily in the body, and often lead to devastating tissue overgrowth. We are studying human stem cells to address fundamental disease mechanisms.Genetic disorders disrupting fat cell energy generation and/or DNA damage repair that cause insulin resistance: We use these to understand lifecourse resilience of human fat tissue, which is crucial for metabolic health. Image People Robert SempleGroup LeaderDominique McCormickPostdoctoral ScientistVahid AslanzadehPostdoctoral ScientistIneke LuijtenPostdoctoral ScientistEleanor McKayPhD studentSheldon D'SilvaPhD studentFatima HamnaPhD studentContactr.semple@ed.ac.uk Robert Semple - Research Information CollaborationsGrzegorz Kudla, University of EdinburghPleasantine Mill, University of EdinburghElizabeth Patton, University of EdinburghAntonella Fidanza, University of EdinburghCataline Vallejos, University of EdinburghRuth Loos, University of CopenhagenStephen O’Rahilly, University of CambridgeDavid Savage, University of CambridgeJulian Sale, MRC LMB, CambridgeGemma Brierley, Anglia Ruskin University, CambridgePartners and FundersWellcome TrustBritish Heart FoundationCLOVES Syndrome CommunityScientific ThemesInsulin resistance, diabetes, lipodystrophy, adipose biology, PI 3-Kinase signalling, mosaic overgrowth disordersTechnology ExpertiseExperimental medicine, human genetics, mouse metabolic phenotyping, insulin signalling, adipocyte models Image Prof Robert Semple, Chair of Translational Molecular Medicine, CMVM Dean of Postgraduate Research Research in a Nutshell Reduced ability of insulin to lower blood glucose is known as insulin resistance. This is common, is closely associated with obesity, and is believed to drive numerous major diseases. We aim to understand how it occurs and how it is linked to diabetes, fatty liver, high blood fat levels, reduced fertility and cancer. To do this we focus on rare and severe disorders caused by changes in individual genes, including severe insulin resistance, low blood glucose, and/or excess tissue growth. We study people with known genetic changes, look for new genetic changes in studies of people and populations, and investigate the changes we find in mice and cells. Specific interests include:Defects of insulin signalling: We use these to test which diseases are caused by lack of insulin action, and which by compensatory increased insulin action. We are systematically studying all possible insulin receptor mutations, and are investigating anti-receptor antibodies as potential treatments for extreme insulin receptor defects.Mutations increasing insulin-like signalling: Activating mutations, especially in the PIK3CA gene, usually occur after conception, are found patchily in the body, and often lead to devastating tissue overgrowth. We are studying human stem cells to address fundamental disease mechanisms.Genetic disorders disrupting fat cell energy generation and/or DNA damage repair that cause insulin resistance: We use these to understand lifecourse resilience of human fat tissue, which is crucial for metabolic health. Image People Robert SempleGroup LeaderDominique McCormickPostdoctoral ScientistVahid AslanzadehPostdoctoral ScientistIneke LuijtenPostdoctoral ScientistEleanor McKayPhD studentSheldon D'SilvaPhD studentFatima HamnaPhD studentContactr.semple@ed.ac.uk HTML CollaborationsGrzegorz Kudla, University of EdinburghPleasantine Mill, University of EdinburghElizabeth Patton, University of EdinburghAntonella Fidanza, University of EdinburghCataline Vallejos, University of EdinburghRuth Loos, University of CopenhagenStephen O’Rahilly, University of CambridgeDavid Savage, University of CambridgeJulian Sale, MRC LMB, CambridgeGemma Brierley, Anglia Ruskin University, CambridgePartners and FundersWellcome TrustBritish Heart FoundationCLOVES Syndrome CommunityScientific ThemesInsulin resistance, diabetes, lipodystrophy, adipose biology, PI 3-Kinase signalling, mosaic overgrowth disordersTechnology ExpertiseExperimental medicine, human genetics, mouse metabolic phenotyping, insulin signalling, adipocyte models This article was published on 2024-09-23
