Search results for "irs2"
showing 10 items of 11 documents
Cyclin-Dependent Kinase 4 Regulates Adult Neural Stem Cell Proliferation and Differentiation in Response to Insulin
2017
Abstract Insulin is one of the standard components used to culture primary neurospheres. Although it stimulates growth of different types of cells, the effects of insulin on adult neural stem cells (NSCs) have not been well characterized. Here, we reveal that insulin stimulates proliferation, but not survival or self-renewal, of adult NSCs. This effect is mediated by insulin receptor substrate 2 (IRS2) and subsequent activation of the protein kinase B (or Akt), leading to increased activity of the G1-phase cyclin-dependent kinase 4 (Cdk4) and cell cycle progression. Neurospheres isolated from Irs2-deficient mice are reduced in size and fail to expand in culture and this impaired proliferati…
Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of …
1999
Aims/hypothesis. The aim of this study was to screen part of the putative promoter sequence in addition to 14 potential phosphotyrosine residues of human IRS-2 for genetic variability which might cause changes in protein expression or function. Furthermore, the potential impact on insulin secretion and sensitivity of a previously identified IRS-2 variant (Gly1057Asp) was analysed Methods. The screenings were carried out by the SSCP-heteroduplex technique on DNA from Type II (non-insulin-dependent) diabetic patients. The impact of the Gly1057Asp variant was analysed in four glucose-tolerant Scandinavian study groups. Results. The results showed no nucleotide substitutions in the promoter seq…
STAT6: its role in interleukin 4-mediated biological functions.
1997
Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to in…
Ink4/Arf locus restores glucose tolerance and insulin sensitivity by reducing hepatic steatosis and inflammation in mice with impaired IRS2-dependent…
2015
Single nucleotide polymorphisms near the Ink4/Arf locus have been associated with type-2 diabetes mellitus. Previous studies indicate a protective role of the locus in the carbohydrate metabolism derangement associated with ageing in wild-type mice. The present study demonstrates that the increased Ink4/Arf locus expression in 1-year-old mice, partially-deficient for the insulin receptor substrate (IRS)2 (Irs2 +/-SuperInk4/Arf mice) ameliorates hepatic steatosis, inflammation and insulin resistance. Irs2 +/-SuperInk4/Arf mice displayed improved glucose tolerance and insulin sensitivity compared with Irs2 +/- mice which were glucose intolerant and insulin resistant compared with age-matched …
Papel de locus Ink4/Arf y del sustrato 2 del receptor de la insulina (IRS2) en la diabetes y la aterosclerosis
2013
En el ratón, la inactivación completa del gen que codifica para el sustrato 2 del receptor de la insulina (Irs2-/-) provoca resistencia a insulina, síndrome metabólico y acelera la aterosclerosis. En la presente tesis se pretende profundizar en los mecanismos moleculares implicados en estos procesos patológicos estudiando (1) la expresión de la ruta de la señalización de la insulina mediada por IRS2 en células mononucleares de sangre periféricas de pacientes con SM sensibles y resistentes a insulina, (2) el efecto de la inactivación parcial de IRS2 sobre el desarrollo de la placa de ateroma en ratones hipercolesterolémicos deficientes en apoE y (3) el efecto del bloqueo de la ruta de la señ…
IRS2 signalling is required for the development of a subset of sensory spinal neurons
2012
Insulin and insulin-like growth factor-I play important roles in the development and maintenance of neurons and glial cells of the nervous system. Both factors activate tyrosine kinase receptors, which signal through adapter proteins of the insulin receptor substrate (IRS) family. Although insulin and insulin-like growth factor-I receptors are expressed in dorsal root ganglia (DRG), the function of IRS-mediated signalling in these structures has not been studied. Here we address the role of IRS2-mediated signalling in murine DRG. Studies in cultured DRG neurons from different embryonic stages indicated that a subset of nerve growth factor-responsive neurons is also dependent on insulin for …
Estudio citoarquitectural de la retina del ratón en relación a la disponibilidad del sustrato del receptor de la insulina (IRS2). Nuevas perspectivas…
2014
Título: Estudio citoarquitectural de la retina del ratón en relación a la disponibilidad del sustrato del receptor de la insulina (IRS2). Nuevas perspectivas para las enfermedades retinianas. Propósito: Investigar los cambios retinianos en los ratones adultos homocigotos para la delección de IRS2 (IRS2-/-) en comparación con ratones control. Metodología: Fueron utilizados en este estudio ratones IRS2-/- de 12 semanas de edad y ratones controles C57BL/6J. Las retinas fueron procesadas para técnicas de inmunohistoquímica, y examinadas al microscopio óptico usando anticuerpos específicos para la identificación de filamentos intermedios de las células gliales (proteína ácida fibrilar glial; GFA…
IRS-2 deficiency impairs NMDA receptor-dependent long-term potentiation
2011
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License.-- et al.
Insulin resistance aggravates atherosclerosis by reducing vascular smooth muscle cell survival and increasing CX3CL1/CX3CR1 axis.
2014
Aims Insulin resistance (IR) is a major risk factor for cardiovascular disease and atherosclerosis. Life-threatening acute events are mainly due to rupture of unstable plaques, and the role of vascular smooth muscle cells (VSMCs) in this process in IR, Type 2 diabetes mellitus, and metabolic syndrome (T2DM/MetS) has not been fully addressed. Therefore, the role of VSMC survival in the generation of unstable plaques in T2DM/MetS and the involvement of inflammatory mediators was investigated. Methods and results Defective insulin receptor substrate 2 (IRS2)-mediated signalling produced insulin-resistant VSMCs with reduced survival, migration, and higher apoptosis than control cells. Silencing…
Role of insulin-like growth factors in autocrine growth of human retinoblastoma Y79 cells.
1996
In this study, we have demonstrated that human retinoblastoma Y79 cells produce insulin-like growth factors (IGFs) type I and type II and release them into the medium. We have also ascertained, by means of competitive studies and cross-linking procedure, that Y79 cells contain the type-I IGF receptor (IGF-IR). Furthermore, surface-bound IGF-I is internalised by the receptor, then degraded to amino acids. Insulin, IGF-I and IGF-II caused down-regulation of IGF-IR; the effect is concentration and time dependant. Scatchard analysis demonstrated that incubation with insulin markedly decreased the binding capacity measured for IGF-I while the apparent Kd value calculated for IGF-I binding was no…