Nearly a century after insulin was discovered, an international team of researchers including 大发娱乐 科学家报告称，他们培育出了世界上最小的企鹅, 完全功能的荷尔蒙, one that combines the potency of human insulin with the fast-acting potential of a venom insulin produced by predatory cone snails. 这一发现, 基于动物研究, could jumpstart the development of insulin treatments capable of improving the lives of those with 糖尿病.
"We now have the capability to create a hybrid version of insulin that works in humans 和 that also appears to have many of the positive attributes of cone snail insulin,” 周鸿杰， Ph.D, a U of U Health assistant professor of biochemistry 和 one of the study's corresponding authors. "That's an important step forward in our quest to make 糖尿病 treatment safer 和 more effective."
这项研究发表在 自然、结构与分子生物学.
As cone snails slither across coral reefs, they are constantly on the prowl for prey. 这些捕鱼的物种中有一些，比如 圆锥geographus, release plumes of toxic venom that contain a unique form of insulin into the surrounding water. The insulin causes fish blood glucose levels to plummet, temporarily paralyzing them. As the fish flounders, the snail emerges from its shell to swallow the subdued victim whole.
在大发娱乐观看一只锥体蜗牛瘫痪并吞下一整条鱼.
在早期的研究中, Chou 和 colleagues discovered that this venomous insulin had many biochemical traits in common with human insulin. Plus, it appears to work faster than the swiftest-acting human insulin currently available.
Faster-acting insulin would diminish the risk of hyperglycemia 和 other serious complications of 糖尿病, 说 海伦娜影响, Ph.D., a study co-author 和 an assistant professor of biomedical sciences at the University of Copenhagen in Denmark. It also could improve the performance of insulin pumps or artificial pancreas devices, 根据需要自动释放胰岛素到体内. "We want to help people with 糖尿病 to more tightly 和 rapidly control their blood sugar,她说
在追求他们的目标, the researchers found that insulin derived from cone snail venom lacks a "hinge" component that causes human insulin to aggregate or clump together so it can be stored in the pancreas. These aggregates must break up into individual molecules before they can begin to work on blood sugar, 这个过程可能需要一个小时. 因为蜗牛胰岛素不会聚集, it is in essence primed 和 ready to work on the body's biochemical machinery almost immediately
感兴趣, the researchers began to investigate ways to transform the insulin that cone snails use as a weapon into a different form: one that people who have Type-1 糖尿病 could use to rapidly restore equilibrium in their bodies.
“大发娱乐有让人类胰岛素更像蜗牛的想法,萨法维说。, 他也是大发娱乐的生物化学副教授. "So, we sought to basically take some of the advantageous properties from the snail 和 graft them onto the human compound."
The researchers thought this was possible because cone snail insulin essentially has the same basic structure or "backbone" as human insulin. However, they faced a dilemma: the snail's insulin is far less potent than human insulin. 事实上, the researchers suspect that humans would require 20 to 30 times more of the cone snail insulin to lower their blood sugar levels.
在这项新的研究中，周和他的同事们试图克服这些问题. 第一个, they used structural biology 和 medicinal chemistry techniques to isolate four amino acids that help the snail insulin bind to the insulin receptor. 然后, they created a truncated version of a human insulin molecule without the region responsible for clumping.
The team integrated modified versions of these amino acids into the human molecule in hopes of creating a hybrid that does not clump 和 binds the human insulin receptor with high potency.
在实验室老鼠的实验中, 这个混合型胰岛素分子, 科学家称之为“迷你胰岛素”," interacted with insulin receptors in ways that cone snail insulin doesn't. These new interactions bound mini-insulin to insulin receptors in the rat's body just as strongly as normal human insulin would. As a result, mini-insulin had the same potency as human insulin but acted faster.
“迷你胰岛素具有巨大的潜力，”周说. “只需要一些战略性的替换, 大发娱乐产生了一个强有力的, 快速作用的分子结构是最小的, 完全活跃的胰岛素. 因为它太小了, 它应该很容易合成, making it a prime c和idate for the development of a new generation of insulin therapeutics."
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除了博士. 周和萨法维, 其他参与这项研究的U of U Health研究人员的标题为, "A structurally minimized yet fully active insulin based on cone-snail venom insulin principles, 是X. 熊,M. M. Disotuar G. Ghabash R. Agrawal X. 王,X. 他,年代. J. 费舍尔,J. Gajewiak和B. 奥利维拉. 这项研究是由 国家糖尿病、消化和肾脏疾病研究所（NIDDK） 和 澳大利亚国家卫生和医学研究委员会.
大发娱乐 provides leading-edge 和 compassionate medicine for a referral area that encompasses 10% of the U.S.包括爱达荷州、怀俄明州、蒙大拿州和内华达州的大部分地区. 是本地区卫生科学研究和教育的中心, U of U Health touts a $356 million research enterprise 和 trains the majority of Utah's physicians 和 more than 1,250 health care providers each year at its Schools of Medicine 和 Dentistry 和 Colleges of Nursing, 药店, 和健康. With more than 20,000 employees, the system includes 12 community clinics 和 four hospitals. 连续10年，uu of U Health一直名列全美大学排名前10位.S. academic medical centers in the rigorous Vizient Quality 和 Accountability Study, 包括达到. 2010年和2016年各1次.