Insulin signaling proteins and their role in regulating sarcoplasmic reticulum calcium-pump (SERCA) function in cardiac and skeletal muscle

这项发现拨款申请已经提交，以确保资金支持一项研究计划，该计划将确定胰岛素是否可以通过直接改变钙转运蛋白的功能特征来影响心脏和骨骼肌的肌肉收缩性。尽管心肌和骨骼肌在许多方面相似，但这些组织具有一些代谢和分子适应，使每个组织都是独特的。例如，在心脏中发现的钙转运蛋白的类型与在骨骼肌中发现的钙转运蛋白不同。由于钙是导致肌肉收缩的重要分子，钙转运蛋白的正常工作对我们的肌肉进行身体活动所需的平稳运动是很重要的。众所周知，胰岛素可以调节人体的血糖。然而，一些科学家已经证明胰岛素信号也可以影响肌肉收缩力。解释这种效应的一种机制与胰岛素信号蛋白直接与肌肉中的钙转运蛋白相互作用有关。这项提议试图建立在这些有趣的观察结果的基础上，通过使用包括培养的心脏和肌肉细胞、分离的大鼠心脏和肌肉或人类骨骼肌在内的模型来确定是否可以看到类似的效果。从这个研究项目中产生的数据将促进我们对调节肌肉收缩力的因素的理解，并将产生关于影响肌肉中钙运输过程的新知识。如果申请成功，这笔资金将确保我的新兴研究项目有足够的运营资金来进行尖端实验，研究胰岛素对调节心脏和骨骼肌收缩力的过程的影响。它还将在经济上支持学生在我的实验室接受培训，使他们能够成为下一代的顶尖科学家。

This Discovery grant application has been submitted to secure funding to support a research program that will determine if insulin can influence muscle contractility in cardiac as well as skeletal muscles by directly altering the functional characteristics of calcium-transport proteins. Although cardiac and skeletal muscles are similar in many aspects, these tissues have several metabolic and molecular adaptations that make each tissue unique. For example, the type of calcium-transport proteins that are found in the heart are different than the calcium-transport proteins found in skeletal muscles. Since calcium is an important molecule that causes muscle to contract, it is important that calcium-transport proteins work properly to allow our muscles to perform the smooth movements required for physical activity. Insulin is most commonly known to regulate blood sugar in humans. However, some scientists have shown that insulin signaling can also influence muscle contractility. One mechanism to explain this effect is associated with the fact that insulin signaling proteins directly interact with calcium-transport proteins in muscle. This proposal seeks to build upon these interesting observations by determining if similar effects can be seen using models that include cultured heart and muscle cells, isolated rat hearts and muscles, or in human skeletal muscle. Data emerging from this research program will advance our understanding of factors that regulate muscle contractility and will generate new knowledge regarding processes that influence calcium transport processes in muscle. If this application is successful, the funding will ensure that my emerging research program has the operating funds to conduct cutting edge experiments looking at the influence insulin exerts on the processes that regulate contractility in the heart as well as in skeletal muscle. It will also financially support students training in my laboratory so they can become the next generation of leading scientists.