Date of Award
Master of Science
Theses & dissertations (Interdisciplinary)
Rudy J. Valentine
A major risk factor for the development of type 2 diabetes is reduced skeletal muscle insulin sensitivity. It is known that exercise and caloric restriction can improve skeletal muscle insulin resistance, but the mechanism by which this occurs is not completely elucidated. The AMP-activated protein kinase (AMPK), is thought to be a major contributor to the metabolic benefits observed after exercise training and caloric restriction. Activation of AMPK in skeletal muscle can have a wide range of effects, one of which is the initiation of macroautophagy (herein referred to as autophagy). Autophagy is the bulk degradation system of the cell and is essential for the maintenance of cellular homeostasis. Another intervention that has been shown to have insulin sensitizing effects and activation of AMPK, is heat treatment. Heat treatment consists of acute bouts of low heat loads. Although high heat loads have been shown to regulate autophagy, whether low heat loads given with heat treatment can regulate autophagy has yet to be investigated. Additionally, the role that autophagy plays in the heat-induced insulin sensitization of skeletal muscle has not been investigated. Thus, the aims for the following studies were to investigate autophagy regulation with heat treatment and to identify what role autophagy may have in the insulin sensitizing effects of heat treatment in insulin resistant skeletal muscle cells.
Here we show that heat treatment activates protein signaling involved in the initiation of autophagy and autophagosome formation in skeletal muscle cells. Additionally, when autophagy was inhibited, heat treatment was able to decrease autophagosomal accumulation. This suggests that heat can increase basal autophagy, and potentially rescue autophagic flux when inhibited. When myotubes were treated with palmitate, insulin signaling decreased, autophagy initiation was blunted, autophagosomal accumulation occurred, and cell stress markers were elevated. Heat treatment was able to reduce some markers of insulin resistance, reduce cell stress markers, and partially drive autophagosomal degradation. When autophagy was inhibited, the mild attenuation of insulin resistance was removed. This suggests that autophagy plays a role in insulin sensitization, and that heat treatment may attenuate insulin resistance, at least partially through the induction of autophagy, but further investigation is necessary to understand the extent or magnitude of this role.
Corey Michael Summers
Summers, Corey Michael, "Impact of acute heat treatment on autophagy and insulin signaling in C2C12 myotubes" (2018). Graduate Theses and Dissertations. 16775.