Frances Ashcroft (Oxford) 2: ATP-sensitive potassium channels and neonatal diabetes: from molecule to malady

Frances Ashcroft (Oxford) 2: ATP-sensitive potassium channels and neonatal diabetes: from molecule to malady

Recording date: 17/01/2018
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Frances Ashcroft and her colleagues have identified mutations in a potassium channel as the cause of neonatal diabetes. Their discovery vastly improved treatment for patients. https://www.ibiology.org/human-disease/neonatal-diabetes/ Talk Overview: In this, her second lecture, Ashcroft expands on what is known about the KATP channel and its role in insulin secretion.  It is an octomeric complex composed of 4 Kir6.2 subunits and 4 SUR1 subunits. ATP binds to both proteins, and changes in metabolically generated ATP couple metabolism to KATP channel activity. Functional studies showed that the KATP channel mutations found in neonatal diabetes impair the ability of ATP to close the channel and stimulate insulin release.  This suggested that drugs that could directly close the KATP channel would stimulate insulin release and might be a good therapy for neonatal diabetes. Sulfonylurea drugs were already known to directly close the KATP channel and have been safely used to treat type 2 diabetes for many years. Based on this knowledge, many patients with neonatal diabetes have now switched from insulin injections to oral sulfonylurea drugs. This has resulted in much better glucose control.  Ashcroft goes on to explain how insights from studying neonatal diabetes have also led to a better understanding of the impact of chronic hyperglycemia in type 2 diabetes. Speaker Biography: Professor Dame Frances Ashcroft is the GlaxoSmithKline Royal Society Research Professor in the Department of Physiology, Anatomy and Genetics, and a Fellow of Trinity College, at the University of Oxford.   Ashcroft received her BA and PhD degrees from Cambridge University and was a post-doctoral fellow at Leicester University and the University of California, Los Angeles. When she set up her own lab at Oxford, Ashcroft began to study how a rise in blood sugar levels leads to the release of insulin from the pancreatic beta cells, and what goes wrong with this process in diabetes. Ashcroft’s more recent research has focused on neonatal diabetes, a rare genetic form of the disease that typically develops soon after birth.  Together with her colleagues, she has shown that mutations in an ATP-sensitive potassium channel in the plasma membrane are responsible for this disease. Understanding the mechanism of action of this potassium channel has allowed many patients to switch from insulin injections to oral drug therapy. In addition, insights gained from the study of neonatal diabetes have implications for the understanding and treatment of type 2 diabetes, a much more common disease. Ashcroft was elected a Fellow of the Royal Society in 1999 and in 2012 she was the European Laureate for the L’Oréal-UNESCO Women in Science Award.  Learn more about Ashcroft’s research here: https://www.dpag.ox.ac.uk/team/frances-ashcroft

Frances Ashcroft (University of Oxford)


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