Author ORCID Identifier

https://orcid.org/0000-0001-8766-4309

Date of Graduation

12-2017

Document Type

Dissertation (PhD)

Program Affiliation

Biochemistry and Molecular Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Rebecca Berdeaux

Committee Member

Vihang Narkar

Committee Member

Guangwei Du

Committee Member

Edgar Walters

Committee Member

Pramod Dash

Abstract

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.

Keywords

SIK1, diabetes, glucose, muscle, PKA, insulin, fat, CREB, AMPK

Available for download on Saturday, December 15, 2018

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