<i>Xenopus laevis</i> insulin receptor substrate IRS‐1 is important for eye development

Bugner, Verena; Aurhammer, Thomas; Kühl, Michael

doi:10.1002/dvdy.22659

Cited by 9 publications

(6 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, a variety of studies suggest that insulin plays a major role in development as a trophic factor [29], [30], [31]. Moreover, insulin receptor substrate-1, the major substrate of the insulin receptor, is necessary for amphibian eye development [32].…”

Section: Discussionmentioning

confidence: 99%

Insulin Stimulated-Glucose Transporter Glut 4 Is Expressed in the Retina

et al. 2012

View full text Add to dashboard Cite

The vertebrate retina is a very metabolically active tissue whose energy demands are normally met through the uptake of glucose and oxygen. Glucose metabolism in this tissue relies upon adequate glucose delivery from the systemic circulation. Therefore, glucose transport depends on the expression of glucose transporters. Here, we show retinal expression of the Glut 4 glucose transporter in frog and rat retinas. Immunohistochemistry and in situ hybridization studies showed Glut 4 expression in the three nuclear layers of the retina: the photoreceptor, inner nuclear and ganglionar cell layers. In the rat retina immunoprecipitation and Western blot analysis revealed a protein with an apparent molecular mass of 45 kDa. 14C-glucose accumulation by isolated rat retinas was significantly enhanced by physiological concentrations of insulin, an effect blocked by inhibitors of phosphatidyl-inositol 3-kinase (PI3K), a key enzyme in the insulin-signaling pathway in other tissues. Also, we observed an increase in 3H-cytochalasin binding sites in the presence of insulin, suggesting an increase in transporter recruitment at the cell surface. Besides, insulin induced phosphorylation of Akt, an effect also blocked by PI3K inhibition. Expression of Glut 4 was not modified in retinas of a type 1 diabetic rat model. To our knowledge, our results provide the first evidence of Glut4 expression in the retina, suggesting it as an insulin- responsive tissue.

show abstract

Section: Discussionmentioning

confidence: 99%

Insulin Stimulated-Glucose Transporter Glut 4 Is Expressed in the Retina

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The major mediators of IGF1R/IR signalling are the insulin receptor substrates (IRS). Loss of IRS1 function in Xenopus embryos affects the expression of the eye marker genes rx1 and pax6 , but not the pan-neural marker gene sox3 26 . These results support our idea that canonical IGF1R signalling does not contribute to the induction of anterior neural tissues.…”

Section: Discussionmentioning

confidence: 99%

Insulin-like factor regulates neural induction through an IGF1 receptor-independent mechanism

Haramoto

Takahashi

Oshima

et al. 2015

Sci Rep

View full text Add to dashboard Cite

Insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) signalling is required for normal embryonic growth and development. Previous reports indicated that the IGF/IGF1R/MAPK pathway contributes to neural induction and the IGF/IGF1R/PI3K/Akt pathway to eye development. Here, we report the isolation of insulin3 encoding a novel insulin-like ligand involved in neural induction. Insulin3 has a similar structure to pro-insulin and mature IGF ligands, but cannot activate the IGF1 receptor. However, similar to IGFs, Insulin3 induced the gene expression of an anterior neural marker, otx2, and enlarged anterior head structures by inhibiting Wnt signalling. Insulin3 are predominantly localised to the endoplasmic reticulum when otx2 is induced by insulin3. Insulin3 reduced extracellular Wnts and cell surface localised Lrp6. These results suggest that Insulin3 is a novel cell-autonomous inhibitor of Wnt signalling. This study provides the first evidence that an insulin-like factor regulates neural induction through an IGF1R-independent mechanism.

show abstract

“…The genes encoding IRS proteins are evolutionarily conserved through the animal kingdom, from worm to human, and a single or multiple IRS paralogous genes are found within a species. In vertebrates, three to four types of genes encoding structurally related IRS proteins (IRS-1, -2, -3, and -4) have been found in many species ( 48 , 49 ). From previous reports and current genome database analyses, the human genome harbors IRS-1, -2, and -4 genes, but it apparently lost the IRS-3 gene during evolution though the mouse genome contains all four IRS genes.…”

Section: Insulin Receptor Substratesmentioning

confidence: 99%

The Novel Functions of High-Molecular-Mass Complexes Containing Insulin Receptor Substrates in Mediation and Modulation of Insulin-Like Activities: Emerging Concept of Diverse Functions by IRS-Associated Proteins

et al. 2015

View full text Add to dashboard Cite

Insulin-like peptides, such as insulin-like growth factors (IGFs) and insulin, induce a variety of bioactivities, such as growth, differentiation, survival, increased anabolism, and decreased catabolism in many cell types and in vivo. In general, IGFs or insulin bind to IGF-I receptor (IGF-IR) or insulin receptor (IR), activating the receptor tyrosine kinase. Insulin receptor substrates (IRSs) are known to be major substrates of receptor kinases, mediating IGF/insulin signals to direct bioactivities. Recently, we discovered that IRSs form high-molecular-mass complexes (referred to here as IRSomes) even without IGF/insulin stimulation. These complexes contain proteins (referred to here as IRSAPs; IRS-associated proteins), which modulate tyrosine phosphorylation of IRSs by receptor kinases, control IRS stability, and determine intracellular localization of IRSs. In addition, in these complexes, we found not only proteins that are involved in RNA metabolism but also RNAs themselves. Thus, IRSAPs possibly contribute to modulation of IGF/insulin bioactivities. Since it is established that disorder of modulation of insulin-like activities causes various age-related diseases including cancer, we could propose that the IRSome is an important target for treatment of these diseases.

show abstract

Xenopus laevis insulin receptor substrate IRS‐1 is important for eye development

Cited by 9 publications

References 61 publications

Insulin Stimulated-Glucose Transporter Glut 4 Is Expressed in the Retina

Insulin Stimulated-Glucose Transporter Glut 4 Is Expressed in the Retina

Insulin-like factor regulates neural induction through an IGF1 receptor-independent mechanism

The Novel Functions of High-Molecular-Mass Complexes Containing Insulin Receptor Substrates in Mediation and Modulation of Insulin-Like Activities: Emerging Concept of Diverse Functions by IRS-Associated Proteins

Contact Info

Product

Resources

About