| [ Summary ] |
Recently, various mouse models, in which genes involved in insulin signaling disruption have been created. These mouse models help us to understand the impact of insulin resistance on those tissues associated with the development of imbalances in energy homeostasis. With the use of Cre-loxP-mediated gene recombination, various tissue-specific insulin receptor knockout mice have been produced. Muscle-specific disruption of the insulin receptor gene did not lead to any alteration in glucose homeostasis. Liver-specific insulin receptor knockout mice exhibited insulin resistance, with mild hyperglycemia, in a fasting state and marked postprandial hyperglycemia. Moreover, analysis of beta cell-specific insulin receptor knockout mice reveled that signals transmitted through the insulin receptor were involved in glucose-induced insulin secretion in beta cells. Both IRS-1 and IRS-2 knockout mice showed insulin resistance; the former exhibited more severe insulin resistance in muscle tissue, whereas the latter were in the liver. Although disruption of the IRS-3 gene did not affect either morphology of adipocytes or glucose homeostasis in vivo, IRS-1/IRS-3 double knockout mice exhibited severe reduction in adipocyte mass, as well as marked insulin resistance and glucose intolerance. Disruption of the IRS-4 gene lead to mild glucose intolerance. It is not currently known which signal disuption, in which organ, reflects the phenotype. |