The development of insulin resistance in Type 2 diabetes: insights from knockout studies.
Diabetes is a common endocrine disorder, primarily characterised by elevated plasma glucose levels. The disease affects all age groups worldwide. Most patients suffer from Type 2 diabetes, which is mainly due to insulin resistance. It is thought that changes in insulin signalling pathways underlie the development of insulin resistance. This article aims to review recent studies that have elucidated the role of individual proteins in these insulin signalling pathways. These studies have been undertaken using two strategies, one employing mice carrying a global null mutation of particular gene-encoding proteins by the homologous recombination method and another strategy using mice with tissue-specific insulin receptor and/or GLUT4 knockout by the Cre-loxP system. The various phenotypes of these knockout mice, and the light they shed on the etiology of insulin resistance, are discussed. By advancing our understanding of the complex molecular mechanisms underlying insulin resistance, these knock-out models may help us to develop more effective treatments for Type 2 diabetes.
MOAC Doctoral Training Centre, University of Warwick, Coventry, UK. R.Pattaranit@warwick.ac.uk
Ratchada
R
Pattaranit
Hugo Antonius
HA
van den Berg
David
D
Spanswick
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D011972:Receptor, Insulin / Q000378:metabolism
D051275:Glucose Transporter Type 4; D011972:Receptor, Insulin; D005947:Glucose