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

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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.