Role of the exon 11 of the insulin receptor gene on insulin binding identified by anti-peptide antibodies

Sesti, Giorgio; Tullio, Antonella N.; Marini, Maria Adelaide; Manera, Ernesto; Borboni, P.; Accili, Domenico; Longhi, Renato; Fusco, Angelo; Lauro, Renato; Montemurro, A.

doi:10.1016/0303-7207(94)90226-7

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…Membranes were blocked in Blocker Casein in PBS (Thermo Scientific, Fisher). Primary antibodies were incubated overnight at 4˚C and were as follows: anti-AKT rabbit polyclonal (1:1000, Cell Signaling Technology, Danvers, MA); anti-phospho-AKT (Ser473) rabbit monoclonal (1:1000, D7F10, Cell Signaling Technology); anti-b-actin mouse monoclonal (1:250, ACTBD11D7, Santa Cruz), as invariant control; b-catenin (1:1000, R&D Systems, Minneapolis, MN); anti-insulin receptor-b rabbit polyclonal (1:250; C-19, Santa Cruz Biotechnology, Santa Cruz, CA); anti-insulin receptor isoform B (rabbit, 1:250) (provided by Giorgio Sesti, Universita Magna Graecia, Catanzaro, Italy) (Sesti et al, 1994); anti-sucrase-isomaltase goat polyclonal (1:500, A-17, Santa Cruz); anti-zonula occludens-1 rabbit monoclonal (1:1000; #8193, Cell Signaling Technology). Secondary antibodies were incubated at room temperature for 2 hours and conjugated to Dylight800 (goat anti-rabbit IgG, goat anti-mouse IgG, donkey anti-goat IgG) or Dylight680 (goat anti-mouse) (1:20,000, Pierce, ThermoScientific Rockford, IL).…”

Section: Western Blottingmentioning

confidence: 99%

Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation

Andres

Simmons

Mah

et al. 2013

Journal of Cell Science

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SummaryDespite evidence for the impact of insulin on intestinal epithelial physiology and pathophysiology, the expression patterns, roles, and regulation of insulin receptor (IR) and IR isoforms in the intestinal epithelium are not well characterized. IR-A is thought to mediate the proliferative effects of insulin or insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be the metabolic receptor for insulin in specialized tissues. This study used a novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial stem cells (IESCs), progenitors, enteroendocrine cells and differentiated lineages, the ApcMin/+ mouse model of precancerous adenoma and normal human intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that there is differential expression of IR-A or IR-B in stem and tumor cells versus differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell proliferation. Our findings provide evidence that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells. IR-B is also reduced in Apc Min/+ tumors and highly tumorigenic CRC cells. These differences in IR-B were accompanied by altered levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR alternative splicing. Forced IR-B expression in subconfluent and undifferentiated Caco-2 cells reduced proliferation and increased biomarkers of differentiation. Our findings indicate that the impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B: IR-A expression levels and provide new evidence for the roles of IR-B to limit proliferation of CRC cells.

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Section: Western Blottingmentioning

confidence: 99%

Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation

Andres

Simmons

Mah

et al. 2013

Journal of Cell Science

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“…The anti-GK antibody was a gift of J. J. Guinovart (Barcelona, Spain). The antibody against IRB isoform (ϩexon 11) was previously described (38).…”

Section: Methodsmentioning

confidence: 99%

PTP1B deficiency increases glucose uptake in neonatal hepatocytes: involvement of IRA/GLUT2 complexes

González-Rodriguez

Nevado²,

Escrivá³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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tion of the liver to glucose utilization is essential to maintain glucose homeostasis. Previous data from protein tyrosine phosphatase (PTP) 1B-deficient mice demonstrated that the liver is a major site for PTP1B action in the periphery. In this study, we have investigated the consequences of PTP1B deficiency in glucose uptake in hepatocytes from neonatal and adult mice. The lack of PTP1B increased basal glucose uptake in hepatocytes from neonatal (3-5 days old) but not adult (10 -12 wk old) mice. This occurs without changes in hexokinase, glucokinase, and glucose 6-phosphatase enzymatic activities. By contrast, the glucose transporter GLUT2 was upregulated at the protein level in neonatal hepatocytes and livers from PTP1B-deficient neonates. These results were accompanied by a significant increase in the net free intrahepatic glucose levels in the livers of PTP1B Ϫ/Ϫ neonates. The association between GLUT2 and insulin receptor (IR) A isoform was increased in PTP1B Ϫ/Ϫ neonatal hepatocytes compared with the wild-type. Indeed, PTP1B deficiency in neonatal hepatocytes shifted the ratio of isoforms A and B of the IR by increasing the amount of IRA and decreasing IRB. Moreover, overexpression of IRA in PTP1B

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“…In turn, Sesti et al revealed that the IgG fraction, isolated from patients suffering from autoimmune hypoglycemia (autoantibodies against insulin receptor) inhibited insulin binding by receptors expressed in cells transfected with vectors and overexpressing E11 -form, but there was no effect on insulin binding in cells transfected with vectors and overexpressing E11 + form [134]. Two years later it was demonstrated that an antibody directed against the amino terminal region encoded by exon 11, was able to inhibit insulin binding by E11 + , but not by E11 -form [135]. Furthermore, other studies have shown that the two insulin receptor isoforms have different ligand with the E11 -variant binding insulin twice as much as a protein encoded by transcript with exon 11 [94,161,162].…”

Section: Insulin Receptor Isoforms and Insr/igf-1r Hybrid Receptorsmentioning

confidence: 99%

“…As mentioned earlier, the two isoforms are differentially expressed in a cell-, tissue-and developmentally-specific manner [38,91,130,135,136]. While both isoforms are expressed in placenta, kidneys, adipose tissue and skeletal muscles, the short variant is expressed in hematopoietic and nervous cells and E11 + isoform dominates in liver [91,130,135,136].…”

Section: Insulin Receptor Isoforms and Insr/igf-1r Hybrid Receptorsmentioning

confidence: 99%

“…While both isoforms are expressed in placenta, kidneys, adipose tissue and skeletal muscles, the short variant is expressed in hematopoietic and nervous cells and E11 + isoform dominates in liver [91,130,135,136]. Furthermore the short form of the receptor is expressed mainly in fetal tissues such as kidneys, skeletal muscles, liver and fibroblasts [38].…”

Section: Insulin Receptor Isoforms and Insr/igf-1r Hybrid Receptorsmentioning

confidence: 99%

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Insulin Receptor and its Relationship with Different Forms of Insulin Resistance

Rojek¹,

Niedziela²

2010

Advances in Cell Biology

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Summary:Insulin plays an important role in maintaining the whole organism's homeostasis. The presence of insulin receptors in all vertebrates and invertebrates cells reflects the diversity of regulatory processes in which this hormone is involved. Furthermore, many different factors may influence the level of insulin receptor expression. These factors include e.g. the sole insulin or stage of development. Mutations in the receptor may lead to the development of insulin resistance. These mutations differ in the level of severity and are frequently associated with diabetes mellitus, hypertension, cardiovascular disorders, heart failure, metabolic syndrome and infertility in women. More than 50 mutations in insulin receptor gene have already been characterized. These mutations are associated with rare forms of insulin resistance like leprechaunism, insulin resistance type A or Rabson-Mendenhall syndrome. Molecular analysis of insulin receptor gene may lead to a better understanding of molecular mechanisms underlying various types of insulin resistance and help to develop more efficient treatment.

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Role of the exon 11 of the insulin receptor gene on insulin binding identified by anti-peptide antibodies

Cited by 11 publications

References 30 publications

Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation

Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation

PTP1B deficiency increases glucose uptake in neonatal hepatocytes: involvement of IRA/GLUT2 complexes

Insulin Receptor and its Relationship with Different Forms of Insulin Resistance

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