Exercise- and insulin-stimulated muscle glucose transport: distinct mechanisms of regulation.
In mammals, skeletal muscle is the primary target for the stimulation of glucose transport by a variety of activators. These include the hormone insulin and stimuli which increase energy demand such as exercise, hypoxia, and challenges to the oxidative chain. While it is known that both stimuli rapidly elevate glucose uptake into muscle by signalling the translocation of glucose transporters from intracellular stores to the plasma membrane, there are numerous contrasts between energy stressors and insulin in their mechanisms of glucose transport activation. Exercise and insulin recruit distinct intracellular pools of glucose transporters in skeletal muscle and the maximal effects of contraction and insulin are additive. Activation of phosphatidylinositol 3-kinase (PI3-K) is utilized by insulin to induce glucose transporter translocation, but does not participate in the responses to exercise or hypoxia. These findings suggest that energy stressors utilize different mechanisms from insulin to increase glucose influx; however, how these factors elicit their response is not clear. This review will summarize our current knowledge of these alternative pathways of glucose transport regulation. Emphasis is placed on the use of the mitochondrial uncoupler dinitrophenol to investigate mediators of this alternative signalling pathway in L6 muscle cells, a line used to characterize physiological responses in muscle such as glucose transport.
Programme in Cell Biology, Hospital for Sick Children, Toronto, ON.
Zayna A
ZA
Khayat
Nish
N
Patel
Amira
A
Klip
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology; D015444:Exercise / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000502:physiology*; D009004:Monosaccharide Transport Proteins / Q000502:physiology; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; D011494:Protein Kinases; D011493:Protein Kinase C; D000091162:AMP-Activated Protein Kinase Kinases; D005947:Glucose