Multiple Mechanisms of Regulating Glucose Transporters and Glucose Transport in Skeletal Muscle Cells PDF Download

Author: Zayna A. Khayat
Publisher:
ISBN:
Category :
Languages : en
Pages :

Get Book Here

Book Description
Glucose is a universal energy substrate of mammalian cells. The Thesis examines the two main pathways of regulating glucose transport in muscle cells--insulin and the metabolic demand pathway. Insulin and the mitochondrial uncoupler dinitrophenol (DNP) were used to stimulate these two pathways in L6 muscle cells in order to dissect differences involving 3 major cellular regulatory pathways: (1) the actin cytoskeleton and temporal spatial regulation of signals and glucose transporters; (2) signalling pathways activated by these stimuli; and (3) cellular mechanisms controlling chronic glucose transporter expression. The results demonstrate that insulin provokes a rapid and marked aggregation of filamentous actin into structures that provide the coordinates for the insulin-derived signals to meet glucose transporter organelles, and direct their insertion into membrane ruffles. The results also reveal that, in contrast to insulin, DNP-stimulated glucose uptake largely depends on cytosolic Ca2+ and Ca2+-sensitive PKCs, but likely does not engage the fuel sensing enzyme AMPK. Finally, insulin and DNP were shown to elicit different long-term effects on glucose transporter expression: whereas prolonged exposure to insulin increases glucose transporter biosynthesis, chronic exposure to DNP increases the half-life of the glucose transporters in an isoform-specific manner. By uncovering the different cellular factors accessed by insulin and DNP to control glucose transport, the Thesis enhances our understanding of the diverse means employed by the muscle cell to control glucose homeostasis, and may have implications for the therapeutic treatment of diseases associated with impaired glucose utilization, such as Type 2 diabetes.