Signal integration and the specificity of insulin action.
Insulin is a potent metabolic hormone essential for the maintenance of normal circulating blood glucose level in mammals. The physiologic control of glucose homeostasis results from a balance between hepatic glucose release (glycogenolysis and gluconeogenesis) and dietary glucose absorption versus skeletal muscle and adipose tissue glucose uptake and disposal. Disruption of this delicate balance either through defects in insulin secretion, liver glucose output, or peripheral tissue glucose uptake results in pathophysiological states of insulin resistance and diabetes. In particular, glucose transport into skeletal muscle and adipose tissue is the rate-limiting step in glucose metabolism and reduction in the efficiency of this process (insulin resistance) is one of the earliest predictors for the development of Type II diabetes. Importantly, recent studies have directly implicated an impairment in insulin receptor signal transduction as the prime mechanism for peripheral tissue insulin resistance. In this review, we have focused on recent developments in our understanding of the molecular mechanisms and signal transduction pathways that insulin utilizes to specifically regulate glucose uptake. The detailed understanding of these events will provide a conceptual framework for the development of new therapeutic targets to treat this chronic and debilitating disease process.
Kanzaki
M
M
Department of Physiology & Biophysics, The University of Iowa, Iowa City 52242, USA.
Pessin
J E
JE
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; D019869:Phosphatidylinositol 3-Kinases