Preserved pancreatic β-cell development and function in mice lacking the insulin receptor-related receptor

T Kitamura, Y Kido, S Nef, J Merenmies… - … and Cellular Biology, 2001 - Taylor & Francis
T Kitamura, Y Kido, S Nef, J Merenmies, LF Parada, D Accili
Molecular and Cellular Biology, 2001Taylor & Francis
Receptors of the insulin/insulinlike growth factor (IGF) family have been implicated in the
regulation of pancreatic β-cell growth and insulin secretion. The insulin receptor-related
receptor (IRR) is an orphan receptor of the insulin receptor gene (Ir) subfamily. It is
expressed at considerably higher levels in β cells than either insulin or IGF-1 receptors, and
it has been shown to engage in heterodimer formation with insulin or IGF-1 receptors. To
address whether IRR plays a physiologic role in β-cell development and regulation of insulin …
Receptors of the insulin/insulinlike growth factor (IGF) family have been implicated in the regulation of pancreatic β-cell growth and insulin secretion. The insulin receptor-related receptor (IRR) is an orphan receptor of the insulin receptor gene (Ir) subfamily. It is expressed at considerably higher levels in β cells than either insulin or IGF-1 receptors, and it has been shown to engage in heterodimer formation with insulin or IGF-1 receptors. To address whether IRR plays a physiologic role in β-cell development and regulation of insulin secretion, we have characterized mice lacking IRR and generated a combined knockout of Irand Irr. We report that islet morphology, β-cell mass, and secretory function are not affected in IRR-deficient mice. Moreover, lack of IRR does not impair compensatory β-cell hyperplasia in insulin-resistant Ir+/− mice, nor does it affect β-cell development and function in Ir−/− mice. We conclude that glucose-stimulated insulin secretion and embryonic β-cell development occur normally in mice lacking Irr.
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