Hyperinsulinemia is associated with increased soluble insulin receptors release from hepatocytes

Marcia Hiriart, Carmen Sanchez-Soto, Carlos Manlio Diaz-Garcia, Diana T. Castanares, Morena Avitia, Myrian Velasco, Jaime Mas-Oliva, Marina Macias-Silva, Clicerio González-Villalpando, Blanca Delgado-Coello, Marcela Sosa-Garrocho, Román Vidaltamayo, Deyanira Fuentes-Silva

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

It has been generally assumed that insulin circulates freely in blood. However it can also interact with plasma proteins. Insulin receptors are located in the membrane of target cells and consist of an alpha and beta subunits with a tyrosine kinase cytoplasmic domain. The ectodomain, called soluble insulin receptor (SIR) has been found elevated in patients with diabetes mellitus. We explored if insulin binds to SIRs in circulation under physiological conditions and hypothesize that this SIR may be released by hepatocytes in response to high insulin concentrations. The presence of SIR in rat and human plasmas and the culture medium of hepatocytes was explored using Western blot analysis. A purification protocol was performed to isolated SIR using affinity, gel filtration, and ion exchange chromatographies. A modified reverse hemolytic plaque assay was used to measure SIR release from cultured hepatocytes. Incubation with 1 nmol l-1insulin induces the release of the insulin receptor ectodomains from normal rat hepatocytes. This effect can be partially prevented by blocking protease activity. Furthermore, plasma levels of SIR were higher in a model of metabolic syndrome, where rats are hyperinsulinemic. We also found increased SIR levels in hyperinsulinemic humans. SIR may be an important regulator of the amount of free insulin in circulation. In hyperinsulinemia, the amount of this soluble receptor increases and this could lead to higher amounts of insulin bound to this receptor, rather than free insulin, which is the biologically active form of the hormone. This observation could enlighten the mechanisms of insulin resistance. © 2014 Hiriart, Sanchez-Soto, Diaz-Garcia, Castanares, Avitia, Velasco, Mas-Oliva, Macias-Silva, González-Villalpando, Delgado-Coello, Sosa-Garrocho, Vidaltamayo and Fuentes-Silva.
Original languageEnglish
JournalFrontiers in Endocrinology
DOIs
Publication statusPublished - 1 Jan 2014

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Insulin Receptor
Hyperinsulinism
Hepatocytes
Insulin
Ion Exchange Chromatography
Protein-Tyrosine Kinases
Gel Chromatography
Culture Media
Insulin Resistance
Blood Proteins
Diabetes Mellitus
Peptide Hydrolases

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism

Cite this

Hiriart, M., Sanchez-Soto, C., Diaz-Garcia, C. M., Castanares, D. T., Avitia, M., Velasco, M., ... Fuentes-Silva, D. (2014). Hyperinsulinemia is associated with increased soluble insulin receptors release from hepatocytes. Frontiers in Endocrinology. https://doi.org/10.3389/fendo.2014.00095
Hiriart, Marcia ; Sanchez-Soto, Carmen ; Diaz-Garcia, Carlos Manlio ; Castanares, Diana T. ; Avitia, Morena ; Velasco, Myrian ; Mas-Oliva, Jaime ; Macias-Silva, Marina ; González-Villalpando, Clicerio ; Delgado-Coello, Blanca ; Sosa-Garrocho, Marcela ; Vidaltamayo, Román ; Fuentes-Silva, Deyanira. / Hyperinsulinemia is associated with increased soluble insulin receptors release from hepatocytes. In: Frontiers in Endocrinology. 2014.
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author = "Marcia Hiriart and Carmen Sanchez-Soto and Diaz-Garcia, {Carlos Manlio} and Castanares, {Diana T.} and Morena Avitia and Myrian Velasco and Jaime Mas-Oliva and Marina Macias-Silva and Clicerio Gonz{\'a}lez-Villalpando and Blanca Delgado-Coello and Marcela Sosa-Garrocho and Rom{\'a}n Vidaltamayo and Deyanira Fuentes-Silva",
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Hiriart, M, Sanchez-Soto, C, Diaz-Garcia, CM, Castanares, DT, Avitia, M, Velasco, M, Mas-Oliva, J, Macias-Silva, M, González-Villalpando, C, Delgado-Coello, B, Sosa-Garrocho, M, Vidaltamayo, R & Fuentes-Silva, D 2014, 'Hyperinsulinemia is associated with increased soluble insulin receptors release from hepatocytes', Frontiers in Endocrinology. https://doi.org/10.3389/fendo.2014.00095

Hyperinsulinemia is associated with increased soluble insulin receptors release from hepatocytes. / Hiriart, Marcia; Sanchez-Soto, Carmen; Diaz-Garcia, Carlos Manlio; Castanares, Diana T.; Avitia, Morena; Velasco, Myrian; Mas-Oliva, Jaime; Macias-Silva, Marina; González-Villalpando, Clicerio; Delgado-Coello, Blanca; Sosa-Garrocho, Marcela; Vidaltamayo, Román; Fuentes-Silva, Deyanira.

In: Frontiers in Endocrinology, 01.01.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hyperinsulinemia is associated with increased soluble insulin receptors release from hepatocytes

AU - Hiriart, Marcia

AU - Sanchez-Soto, Carmen

AU - Diaz-Garcia, Carlos Manlio

AU - Castanares, Diana T.

AU - Avitia, Morena

AU - Velasco, Myrian

AU - Mas-Oliva, Jaime

AU - Macias-Silva, Marina

AU - González-Villalpando, Clicerio

AU - Delgado-Coello, Blanca

AU - Sosa-Garrocho, Marcela

AU - Vidaltamayo, Román

AU - Fuentes-Silva, Deyanira

PY - 2014/1/1

Y1 - 2014/1/1

N2 - It has been generally assumed that insulin circulates freely in blood. However it can also interact with plasma proteins. Insulin receptors are located in the membrane of target cells and consist of an alpha and beta subunits with a tyrosine kinase cytoplasmic domain. The ectodomain, called soluble insulin receptor (SIR) has been found elevated in patients with diabetes mellitus. We explored if insulin binds to SIRs in circulation under physiological conditions and hypothesize that this SIR may be released by hepatocytes in response to high insulin concentrations. The presence of SIR in rat and human plasmas and the culture medium of hepatocytes was explored using Western blot analysis. A purification protocol was performed to isolated SIR using affinity, gel filtration, and ion exchange chromatographies. A modified reverse hemolytic plaque assay was used to measure SIR release from cultured hepatocytes. Incubation with 1 nmol l-1insulin induces the release of the insulin receptor ectodomains from normal rat hepatocytes. This effect can be partially prevented by blocking protease activity. Furthermore, plasma levels of SIR were higher in a model of metabolic syndrome, where rats are hyperinsulinemic. We also found increased SIR levels in hyperinsulinemic humans. SIR may be an important regulator of the amount of free insulin in circulation. In hyperinsulinemia, the amount of this soluble receptor increases and this could lead to higher amounts of insulin bound to this receptor, rather than free insulin, which is the biologically active form of the hormone. This observation could enlighten the mechanisms of insulin resistance. © 2014 Hiriart, Sanchez-Soto, Diaz-Garcia, Castanares, Avitia, Velasco, Mas-Oliva, Macias-Silva, González-Villalpando, Delgado-Coello, Sosa-Garrocho, Vidaltamayo and Fuentes-Silva.

AB - It has been generally assumed that insulin circulates freely in blood. However it can also interact with plasma proteins. Insulin receptors are located in the membrane of target cells and consist of an alpha and beta subunits with a tyrosine kinase cytoplasmic domain. The ectodomain, called soluble insulin receptor (SIR) has been found elevated in patients with diabetes mellitus. We explored if insulin binds to SIRs in circulation under physiological conditions and hypothesize that this SIR may be released by hepatocytes in response to high insulin concentrations. The presence of SIR in rat and human plasmas and the culture medium of hepatocytes was explored using Western blot analysis. A purification protocol was performed to isolated SIR using affinity, gel filtration, and ion exchange chromatographies. A modified reverse hemolytic plaque assay was used to measure SIR release from cultured hepatocytes. Incubation with 1 nmol l-1insulin induces the release of the insulin receptor ectodomains from normal rat hepatocytes. This effect can be partially prevented by blocking protease activity. Furthermore, plasma levels of SIR were higher in a model of metabolic syndrome, where rats are hyperinsulinemic. We also found increased SIR levels in hyperinsulinemic humans. SIR may be an important regulator of the amount of free insulin in circulation. In hyperinsulinemia, the amount of this soluble receptor increases and this could lead to higher amounts of insulin bound to this receptor, rather than free insulin, which is the biologically active form of the hormone. This observation could enlighten the mechanisms of insulin resistance. © 2014 Hiriart, Sanchez-Soto, Diaz-Garcia, Castanares, Avitia, Velasco, Mas-Oliva, Macias-Silva, González-Villalpando, Delgado-Coello, Sosa-Garrocho, Vidaltamayo and Fuentes-Silva.

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M3 - Article

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

SN - 1664-2392

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