Regulation of glucose transport in human skeletal muscle.
Glucose transport, the rate limiting step in glucose metabolism in skeletal muscle, is mediated by insulin-sensitive glucose transporter 4 (GLUT4) and can be activated in skeletal muscle by two separate and distinct signalling pathways: one stimulated by insulin and the second by muscle contractions. Skeletal muscle is the principal tissue responsible for insulin-stimulated glucose disposal and thus the major site of peripheral insulin resistance. Impaired glucose transport in skeletal muscle leads to impaired whole body glucose uptake, and contributes to the pathogenesis of Type 2 diabetes mellitus. A combination of genetic and environmental factors is likely to contribute to the pathogenesis of Type 2 diabetes mellitus; however, the primary defect is still unknown. Intense efforts are underway to define the molecular mechanisms that regulate glucose metabolism in insulin sensitive tissues. This review will present our current understanding of mechanisms regulating glucose transport in skeletal muscle in humans. Elucidation of the pathways involved in the regulation of glucose homeostasis will offer insight into the pathogenesis of insulin resistance and Type 2 diabetes mellitus and may lead to the identification of biochemical entry points for drug intervention to improve glucose homeostasis.
Koistinen
H A
HA
Department of Clinical Physiology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Zierath
J R
JR
D000091162:AMP-Activated Protein Kinase Kinases; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D015444:Exercise / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000502:physiology; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D000091162:AMP-Activated Protein Kinase Kinases; D005947:Glucose; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; C495692:SLC2A4 protein, human