Seven-year-old Foster's fingertips are so calloused from pricking them that he now draws blood from the sides of his fingers instead. 他的母亲崔西娅说，下一个是他的脚趾. 被诊断为 1型糖尿病（T1D） 十个月大的时候, Tricia started turning some of her son's care over to him as soon as he was able, 从四岁开始. 今天, that means checking his blood sugar eight to ten times each day and, 在崔茜卡的监督下, 需要的时候给自己打一针胰岛素. It's a lot to expect from a young boy, but his life depends on it.
For patients with 1型糖尿病（T1D）, the round-the-clock self-care is hard enough. 更糟糕的是, a miscalculation or lapse in regimen can cause blood sugar levels to rise too high (hyperglycemia), 可能导致心脏病, 失明和其他长期并发症, 或者降得太低（低血糖）, which in the worst cases can result in coma or even death.
To mitigate the dangers inherent to insulin dosing, a University of Utah biochemist and fellow scientists have created Ins-PBA-F, a long-lasting "smart" insulin that self-activates when blood sugar soars. Tests on mouse models for type 1 糖尿病 show that one injection works for a minimum of 14 hours, during which time it can repeatedly and automatically lower blood sugar ils after mice are given amounts of sugar comparable to what they would consume at mealtime.
Ins-PBA-F, 行动更迅速, 而且能更好地降低血糖, 比长效地地米胰岛素要好, 以Levemir的名义销售. 事实上, the speed and kinetics of touching down to safe blood glucose levels are identical in diabetic mouse models treated with Ins-PBA-F and in healthy mice whose blood sugar is regulated by their own insulin. 一项显示这些发现的研究发表在2月11日. 9 in PNAS早期版.
"This is an important advance in insulin therapy," says co-first author Danny Chou, Ph.D., USTAR investigator and assistant professor of biochemistry at the University of Utah. "Our insulin derivative appears to control blood sugar better than anything that is available to 糖尿病 patients right now." He will continue evaluating the long-term safety and efficacy of Ins-PBA-F. The insulin derivative could reach Phase 1 human clinical trials in two to five years.
“目前, there is no clinically approved glucose-responsive modified insulin,马修·韦伯说, Ph.D.，与Chou和Benjamin Tang博士共同第一作者.D., who performed the work together while postdoctoral fellows at MIT in collaboration with senior authors and MIT professors Robert Langer, Ph.D.和丹尼尔·安德森博士.D. "The development of such an approach could contribute to greater therapeutic autonomy for diabetic patients."
The hallmark symptom of 糖尿病 is inadequate control of blood sugar. 这种缺陷在1型糖尿病中最为明显, which develops when insulin-producing beta-cells of the pancreas are destroyed. 没有胰岛素, there is no way to shuttle sugar out of the blood and into cells, 它在哪里被用作能源. T1D patients depend on daily insulin injections for survival.
Despite advances in 糖尿病 treatment such as insulin pumps and the development of four types of insulin, patients must still manually adjust how much insulin they take on a given day. Blood sugar levels vacillate widely depending on a number of factors such as what someone chooses to eat and whether they exercise.
A glucose-responsive insulin that is automatically activated when blood sugar levels are high would eliminate the need for additional boosts of insulin, and reduce the dangers that come with inaccurate dosing. Various such "smart" insulins under development typically incorporate a protein-based barrier, 如凝胶或涂层, 当血糖较低时，它会抑制胰岛素. 然而, such biologically based components are often sources of trouble, provoking unwanted side effects such as an immune response.
Ins-PBA-F differs in that it was created by chemically modifying insulin directly. Ins-PBA-F consists of a long-acting insulin derivative that has a chemical moiety, 苯硼酸（PBA）, 添加到一端. 正常情况下, Ins-PBA-F binds to serum proteins that circulate in the bloodstream, 阻断其活动. 当血糖水平高的时候, 葡萄糖与PBA结合, which acts like a trigger to release Ins-PBA-F so it can get to work.
"Before, a ‘smart' insulin really meant delivering insulin differently," says Chou. "Ins-PBA-F fits the true definition of ‘smart' insulin, 胰岛素本身对葡萄糖有反应吗. 它是同类中的第一艘."
Chou explains that because Ins-PBA-F is a chemically modified version of a naturally occurring hormone, he thinks it is likely to be safe enough to use on a daily basis, similar to other insulin derivatives that are on the market today.
"My goal is to make life easier, and safer for diabetics," he says.
这项工作得到了Leona M. 和Harry B. 赫尔姆斯利慈善信托基金, 塔伊巴蒂家族基金会, 美国国立卫生研究院, 以及青少年糖尿病研究基金会.
Glucose-responsive胰岛素 activity by covalent modification with aliphatic phenylboronic acid conjugates. 周鸿杰，Matthew J. 本杰明·C·韦伯. 艾米·唐. 林，Lavanya S. Thapa, David Deng, Jonathan V. 阿贝尔. 科蒂纳斯，罗伯特·兰格和丹尼尔·安德森. PNAS早期版，2月. 9, 2015
智能，葡萄糖反应胰岛素
University of Utah biochemists and fellow scientists have developed a smart insulin that self-activates in response to blood sugar levels. 血糖高的时候, 胰岛素变得活跃, 迅速恢复正常血糖水平. 一针智能胰岛素, 叫Ins-PBA-F, can repeatedly and automatically normalize blood sugar levels over a minimum of 14 hours in mice with a type 1 糖尿病-like condition. Scientists are now developing the modified insulin into a therapy suitable for human use. Doing so would greatly improve the health and quality of life for diabetics.