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Understanding the pathophysiology

Watch the video to learn how the release of insulin from pancreatic beta cells is regulated, and why sulphonylurea tablets are an effective treatment.
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Beta cells are unique cells in the pancreas that produce, store, and release the hormone insulin. Insulin is secreted in response to rising blood glucose levels following a meal and promotes the uptake of glucose by tissues, particularly the liver, muscles and adipose tissue. This is achieved by the classical pathway of insulin secretion. Glucose enters the beta cell via the GLUT2 glucose transporter. Once inside, glucose is metabolised, resulting in an increase in the concentration of ATP. ATP then binds to the potassium channel, which results in channel closure and prevents the movement of potassium ions out of the cell. Consequently, the cell membrane depolarises, opening the voltage-dependent calcium channel and allowing calcium and ions to enter the cell.
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This triggers a cascade of events which leads to the release of insulin from the cell. The potassium channel consists of four SUR1 subunits and four Kir6.2 subunits. SUR1 is encoded by the ABCC8 gene and Kir6.2 by the KCNJ11 gene. Activating mutations in these genes prevent the closure of the potassium channel in response to elevated ATP, therefore breaking the link between blood glucose concentration and insulin secretion. This results in neonatal diabetes. A group of drugs called sulphonylurea work by binding to the SUR1 subunit of the potassium channel and closing the channel independently of ATP. Individuals with neonatal diabetes due to a potassium channel mutation can transfer from daily insulin injections to sulphonylura tablets.
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This results in improved glycemic control and quality of life. Genetic testing is therefore essential for all individuals diagnosed with neonatal diabetes, as mutations within the potassium channel genes are identified in over 40% of cases.
In this video, we learn how the release of insulin from pancreatic beta cells is regulated. We will find out how mutations in the genes encoding the potassium channel subunits cause neonatal diabetes and why sulphonylurea tablets are an effective treatment for these patients.
Beta cells are unique cells in the pancreas that produce, store and release the hormone insulin. Insulin is secreted in response to rising blood glucose levels following a meal and promotes the uptake of glucose by tissues, particularly the liver, muscles and adipose tissue.
This is achieved by the ‘classical pathway’ of insulin secretion.
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Genomic Medicine: Transforming Patient Care in Diabetes

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