Proteolytic processing of the insulin receptor beta subunit is associated with insulin-induced receptor down-regulation

Knutson, Victoria P.

doi:10.1016/s0021-9258(18)98457-7

Cited by 24 publications

(4 citation statements)

References 35 publications

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“…From these data, it can be suggested that the reduction in the phosphorylation of the insulin receptor was caused by the decrease in insulin receptor expression. In terms of the time scale at which the downregulation occurred, the results from the present work are in agreement with in vitro studies in cells derived from other tissues like 3T3-C2 fibroblasts (Treadway et al, 1989), murine fibroblasts (Knutson, 1991;Knutson et al, 1983) and 3T3-L1 adipocytes (Ronnett et al, 1982).…”

Section: Insulinsupporting

confidence: 91%

Molecular mechanisms of insulin resistance in glucagon-producing alpha cells

Aguirre¹

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Section: Insulinsupporting

confidence: 91%

Molecular mechanisms of insulin resistance in glucagon-producing alpha cells

Aguirre¹

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“…In contrast, upon long lasting hyperinsulinemias, such as that observed in genetically obese Zucker rats, total cellular receptor number in liver is decreased while receptor number in endosomes is increased (Amessou et al, 2009). In Zucker rats, an increase in insulin receptor degradation accounts for the decrease in receptor expression (Amessou et al, 2009), as it does in isolated fibroblasts (Knutson, 1991b), and results in insulin resistance (Knutson et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted October 1, 2023. ; https://doi.org/10.1101/2023.09.07.498136 doi: bioRxiv preprint hyperinsulinemias, such as that observed in genetically obese Zucker rats, total cellular receptor number in liver is decreased while receptor number in endosomes is increased (Amessou et al, 2009). In Zucker rats, an increase in insulin receptor degradation accounts for the decrease in receptor expression (Amessou et al, 2009), as it does in isolated fibroblasts (Knutson, 1991b), and results in insulin resistance (Knutson et al, 1995). Ubiquitination of insulin receptor subunits by the E3 ubiquitin ligases c-Cbl (Ahmed et al, 2000), MG53 (Song et al, 2013) and March1 (Nagarajanet al, 2015), has been implicated in receptor degradation and inhibition of insulin signaling in liver and cultured cells.…”

Section: Introductionmentioning

confidence: 99%

Revisiting the trafficking of insulin and its receptor in rat liver:in vivoand cell-free studies

Tahiri,

Fouque,

Postel-Vinay

et al. 2023

Preprint

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Endosomes are the main locus where, upon endocytosis in liver cells, insulin and the activated insulin receptor accumulate and insulin is degraded. In this study, ligand and receptor pathways in rat liver have been revisited using analytical subcellular fractionation. Density gradient analysis of microsomal and light mitochondrial fractions confirmed that, upon in vivo uptake into liver, radiolabeled insulin was rapidly translocated from plasma membranes to endosomes. Internalized radiolabeled proinsulin and biotinylated insulin, which are less degraded than insulin, were in part transferred from endosomes to lysosomes. Following injection of native insulin, receptor and ligand were also both translocated from the plasma membrane to endosomes. Receptor translocation was progressively reversed and neither its endocytosis nor its recycling were affected by cycloheximide treatment. Fractionation of endosomes on density gradients showed that the receptor was recovered at low density, whereas insulin progressively migrated towards a higher density at the position of acid phosphatase. On sodium dodecyl sulfate polyacrylamide gels, insulin receptor alpha and beta subunits were identified in plasma membrane, endosomal and lysosomal fractions by affinity crosslinking and Western immunoblotting, respectively. Following insulin treatment, receptor expression rapidly decreased in plasma membranes while increasing in endosomes. In a cell free system, labeled insulin was in part transferred from endosomes to lysosomes, as was, with organelle content mixing, labeled biotinylated insulin. It is concluded that, upon endocytosis, the insulin receptor progressively segregates from its ligand, and that neither endocytosis no recycling of the receptor requires protein synthesis.

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“…Tanto em animais como em cultura de células a estimulação crônica com insulina promove dessensibilização e diminuição da regulação da sinalização insulínica (INOUE, CHEATHAM et al 1996). Isto se deve em parte pela internalização e degradação Discussão do receptor de insulina, assim como por diminuição da atividade de substratos intracelulares, como o IRS-1 (REED, NEWTON et al 1989;KNUTSON 1991;RICE, LIENHARD et al 1992;CHEATHAM, SHOELSON et al 1993).…”

Section: Discussionunclassified

Efeito da administração intracerebroventricular de insulina sobre a excreção urinaria de sodio e vias de sinalização da insulina em hipotalamo de ratos hipertensos

Menegon¹,

Gontijo²

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Proteolytic processing of the insulin receptor beta subunit is associated with insulin-induced receptor down-regulation

Cited by 24 publications

References 35 publications

Molecular mechanisms of insulin resistance in glucagon-producing alpha cells

Molecular mechanisms of insulin resistance in glucagon-producing alpha cells

Revisiting the trafficking of insulin and its receptor in rat liver:in vivoand cell-free studies

Efeito da administração intracerebroventricular de insulina sobre a excreção urinaria de sodio e vias de sinalização da insulina em hipotalamo de ratos hipertensos

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