Enhancement of Insulin Transport Across Primary Rat Alveolar Epithelial Cell Monolayers by Endogenous Cellular Factor(s)

Bahhady, Rana; Kim, Kwang‐Jin; Borok, Zea; Crandall, Edward D.; Shen, Wei‐Chiang

doi:10.1007/s11095-007-9301-9

Cited by 5 publications

(2 citation statements)

References 36 publications

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“…Our present findings indicate that BALF contains a protein factor or factors which enhance(s) transport of insulin across RAECM. We have previously reported a similar observation of enhanced insulin transport mediated by protein factor(s) present in conditioned medium obtained from apical fluid of primary cultured RAECM-II [37]. Observations from both studies highlight the importance of the alveolar epithelium in maintaining lung homeostasis through various mechanisms, including endocytosis [21], and may further explain the high bioavailability of several peptide and protein drugs in vivo.…”

Section: Discussionsupporting

confidence: 57%

Characterization of protein factor(s) in rat bronchoalveolar lavage fluid that enhance insulin transport via transcytosis across primary rat alveolar epithelial cell monolayers

Bahhady

Kim

Borok

et al. 2008

European Journal of Pharmaceutics and Biopharmaceutics

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The aim of this study was to characterize factor(s) in rat bronchoalveolar lavage fluid (BALF) that enhance(s) insulin transport across primary rat alveolar epithelial cell monolayers (RAECM) in primary culture. BALF was concentrated 7.5-fold using the Centricon device and the retentate was used to characterize the factor(s) involved in enhancing apical-to-basolateral transport of intact 125 I-insulin across various epithelial cell monolayers. These factor(s) enhanced transport of intact insulin across type II cell-like RAECM (3-fold increase) and type I cell-like RAECM (2-fold increase), but not across Caco-2 or MDCK cell monolayers. The insulin transport-enhancing factor(s) were temperature-and trypsin-sensitive. The mechanism of enhancement did not seem to involve paracellular transport or fluid-phase endocytosis, since fluxes of sodium fluorescein and FITC-dextran (70 kDa) were not affected by the factor(s) in the apical bathing fluid. BALF enhancement of intact 125 I-insulin transport was abolished at 4°C and in the presence of monensin, suggesting involvement of transcellular pathways. Sephacryl S-200 purification of BALF retentate, followed by LC-MS/MS, indicated that the high molecular weight (>100 kDa) fractions (which show some homology to alpha-1-inhibitor III, murinoglobulin gamma 2, and pregnancyzone protein) appear to facilitate transcellular transport of insulin across RAECM.

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Section: Discussionsupporting

confidence: 57%

Characterization of protein factor(s) in rat bronchoalveolar lavage fluid that enhance insulin transport via transcytosis across primary rat alveolar epithelial cell monolayers

Bahhady

Kim

Borok

et al. 2008

European Journal of Pharmaceutics and Biopharmaceutics

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“…Several studies utilizing a reliable in vitro AT2-like cell monolayer model [ 35 , 47 ] have been previously reported. For example, KGF-treated primary rat AT2 cell monolayers (RAECM-II) exhibit AT2 cell-like morphology (i.e., cuboidal shape) and phenotype (i.e., surfactant proteins and lamellar bodies) with an average cell thickness of ~4.2 µm (~8 times the cell thickness estimated for RAECM-I) [ 35 ] These morphological traits of RAECM-I vs. RAECM-II contribute to the estimated numbers of small (but not large) equivalent pores, which are ~8 times greater in RAECM-I than in RAECM-II.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Passive Solute Transport across Primary Rat Alveolar Epithelial Cell Monolayers

Kim

D’Argenio

et al. 2021

Membranes

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Primary rat alveolar epithelial cell monolayers (RAECM) were grown without (type I cell-like phenotype, RAECM-I) or with (type II cell-like phenotype, RAECM-II) keratinocyte growth factor to assess passive transport of 11 hydrophilic solutes. We estimated apparent permeability (Papp) in the absence/presence of calcium chelator EGTA to determine the effects of perturbing tight junctions on “equivalent” pores. Papp across RAECM-I and -II in the absence of EGTA are similar and decrease as solute size increases. We modeled Papp of the hydrophilic solutes across RAECM-I/-II as taking place via heterogeneous populations of equivalent pores comprised of small (0.41/0.32 nm radius) and large (9.88/11.56 nm radius) pores, respectively. Total equivalent pore area is dominated by small equivalent pores (99.92–99.97%). The number of small and large equivalent pores in RAECM-I was 8.55 and 1.29 times greater, respectively, than those in RAECM-II. With EGTA, the large pore radius in RAECM-I/-II increased by 1.58/4.34 times and the small equivalent pore radius increased by 1.84/1.90 times, respectively. These results indicate that passive diffusion of hydrophilic solutes across an alveolar epithelium occurs via small and large equivalent pores, reflecting interactions of transmembrane proteins expressed in intercellular tight junctions of alveolar epithelial cells.

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Cell-based in vitro models for pulmonary permeability studies

Andrade

Albuquerque

Nascimento

2016

Concepts and Models for Drug Permeability Studies

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Enhancement of Insulin Transport Across Primary Rat Alveolar Epithelial Cell Monolayers by Endogenous Cellular Factor(s)

Abstract: Conditioned medium from type II cell-like monolayer cultures appears to contain protein factor(s) which seem to be involved in facilitating active transcellular transport of insulin across primary cultured RAECM-II.

Cited by 5 publications

References 36 publications

Characterization of protein factor(s) in rat bronchoalveolar lavage fluid that enhance insulin transport via transcytosis across primary rat alveolar epithelial cell monolayers

Characterization of protein factor(s) in rat bronchoalveolar lavage fluid that enhance insulin transport via transcytosis across primary rat alveolar epithelial cell monolayers

Characteristics of Passive Solute Transport across Primary Rat Alveolar Epithelial Cell Monolayers

Cell-based in vitro models for pulmonary permeability studies

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