Ten million Canadians are living with diabetes or pre-diabetes. The Canadian Diabetes Association reports that more than 20 Canadians are newly diagnosed with the disease every hour of every day. It is also the seventh leading cause of death in Canada, with associated health-care costs estimated at nearly $9 billion a year. Type 2 diabetes accounts for 90 per cent of all cases, increasing the risk of blindness, nerve damage, stroke, heart disease and several other serious health conditions.
Insulin secretion from β cells of the pancreatic islets of Langerhans is impaired in type 2 diabetes (T2D). Thus, an amplification or regulation of insulin is needed in such cases. Evidence suggests that metabolic amplification of insulin secretion occurs distally in the secretory pathway, possibly at the calcium dependent exocytotic site. Therefore the regulation or amplification of insulin is an important target for researchers around the world
Now, researchers from the University of Alberta have identified a new molecular pathway that manages the amount of insulin produced by the pancreatic cells, essentially a ‘dimmer’ switch that adjusts how much or how little insulin is secreted when blood sugar increases. The team state that the dimmer appears to be lost in Type 2 diabetes, however, it can be restored and ‘turned back on’, reviving proper control of insulin secretion from islet cells of people with Type 2 diabetes. The opensource study is published in the Journal of Clinical Investigation.
Previous studies show that the canonical mechanism of glucose-stimulated insulin secretion involving increases in metabolism-derived ATP, inhibition of KATP channels, and activation of VDCCs was first introduced more than 30 years ago and remains as a cornerstone mechanism for the triggering of insulin secretion’. The KATP channel mechanism does not define the entire secretory response with multiple metabolic coupling intermediates proposed as factors that amplify the secretory response to a Ca2+ exocytosis-based signal, with the net export of mitochondrial substrates being of great interest.
The current study examined pancreatic islet cells from 99 human organ donors. Results show that the glucose-dependent amplification of exocytosis in human β cells, which is disrupted in type 2 diabetes, requires isocitrate flux through mitochondrial export which generates cytosolic NADPH and GSH. These then act through SENP1 to amplify the exocytosis of insulin, thereby controlling glucose homeostasis. The lab then validated these data findings in a transgenic animal model.
The researchers state that the discovery is a potential game-changer in Type 2 diabetes research, leading to a new way of thinking about the disease and its future treatment. The go on to add that understanding the islet cells in the pancreas that make insulin, how they work, and how they can fail, could lead to new ways to treat the disease, delaying or even preventing diabetes.
The team surmise that although the ability to restore and fix the dimmer switch in islet cells may have been proven on a molecular level, finding a way to translate those findings into clinical use could yet take decades. Despite this the group conclude that the findings show an important new way forward.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
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Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.