Textile cone snail6/3/2023 For diabetes patients this could be life-changing.” The cone snail’s ‘cocktail’ of toxins provides many valuable lessons for drug discovery. This tells us that with further development, the response time could be made even shorter. “Even at this early stage of development, Mini-Ins was able in animal models to lower blood sugar levels as fast as the current best treatments that are in use. “Our findings also showed that Mini-Ins doesn’t activate the related insulin-like growth factor pathways that would increase the risk of cancer – something researchers need to absolutely avoid when developing new insulin treatments for diabetes. “We have completed the translational step from a cone snail venom insulin to a human look-alike, Mini-Ins, that is safe and well-tolerated by the immune system, a vital consideration when developing new diabetes treatments,” Professor Lawrence says. In tests with animal models, the hybrid insulin molecule was found to lower blood sugar rapidly levels after meals. “We call the new hybrid insulin ‘Mini-Ins’, short for mini insulin.” Exciting proof-of-principle “The modified versions of the cone snail amino acids were then integrated into the human insulin molecule with the goal of creating a hybrid that would bind the human insulin receptor with high potency and without the capacity for aggregation. “We then began by creating a shortened version of a human insulin molecule without the region responsible for its aggregation.” Magnetic teeth revealed using quantum imaging “So our team identified four amino acids that help the snail venom insulin bind to the insulin receptor,” Dr Menting says. It would also likely be immunotoxic, which can damage the immune system by destroying immune cells and changing signalling pathways. Picture: WEHIīut although it is faster acting, the cone snail’s insulin is far less potent than human insulin and would not be useful in itself as a therapeutic. Mini-Ins (mini insulin) depicted in magenta and green, lacks the orange segment that in human insulin is responsible for its aggregation. Working with the Australian Synchrotron, the team studied the structure of the cone snail insulin in molecular detail, finding that it had the same basic structure as human insulin but lacked the ‘hinge’ component that causes aggregation. “Just like any engineering project, our study required detailed images of the cone snail insulin to know which ‘design changes’ could be made to improve the effectiveness of human insulin,” Dr Menting says. Working closely with Professor Lawrence at the Walter and Eliza Hall Institute is Dr John Menting. It also could improve the performance of insulin pumps or artificial pancreas devices, which automatically release insulin into the body as needed.” Following cone snail clues “Faster-acting insulin may help diminish the risk of hyperglycemia and other serious complications of diabetes. “Our ultimate aim is to help people with diabetes to control their blood sugar more tightly and rapidly,” Professor Lawrence says. Diabetes occurs when your body doesn’t use insulin properly or doesn’t make enough insulin, so injections of the hormone are needed to help manage glucose levels. The hormone works by stimulating the uptake of glucose into cells muscles can take up glucose to use for immediate energy or it can be stored in the liver as glycogen until needed. The hormone, insulin, is normally released rapidly from the pancreas after a meal, when the level of blood sugar - glucose - is high. These aggregates must break up into individual molecules before they can begin to work on blood sugar, a process that can take up to an hour when insulin is used by diabetic patients.” Faster-acting insulin may help diminish the risk of high blood sugar and other serious complications of diabetes. He explains that “the problem with human insulin is that it needs to aggregate to be stored in the pancreas. “Essentially, we wanted to take the fast-acting nature of the snail venom and combine it with the therapeutic properties of human insulin,” Professor Lawrence says. Professor Mike Lawrence, WEHI’s lead researcher on the study, has been investigating the structure of insulins and their function for almost two decades. COMBINING TRAITS OF HUMAN AND SEA SNAIL INSULIN The research is a collaboration between the Walter and Eliza Hall Institute of Medical Research (WEHI) and the University of Utah, along with researchers from the University of Melbourne, La Trobe University, Flinders University and Monash Institute of Pharmaceutical Sciences. In the hope of improving diabetes treatment, Melbourne scientists are focusing on the blood sugar function of the venom.īy creating a modified form of human insulin, they have successfully incorporated the ultra fast-acting properties of cone snail venom insulin from the species Conus geographus.
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