Author ORCID Identifier
Date of Graduation
Biochemistry and Molecular Biology
Doctor of Philosophy (PhD)
Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this kinase. Herein, evidence is provided demonstrating that skeletal muscle SIK1 regulates insulin sensitivity and blood glucose concentrations through mechanism(s) independent of the canonical insulin pathway. Our research addresses many previously unanswered questions about SIK1 action in metabolism and positions SIK1 as a potential therapeutic target for the treatment of metabolic disorders, such as type 2 diabetes, while provoking new questions for future research.
SIK1, diabetes, glucose, muscle, PKA, insulin, fat, CREB, AMPK
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