ABC transporters at the blood–brain barrier

References

• Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–185.
   PubMed Web of Science ®Google Scholar
• Abbott NJ. Dynamics of CNS barriers: evolution, differentiation, and modulation. Cell Mol Neurobiol. 2005;25(1):5–23.
   PubMed Web of Science ®Google Scholar
• Hermann DM, Bassetti CL. Implications of ATP-binding cassette transporters for brain pharmacotherapies. Trends Pharmacol Sci. 2007;28(3):128–134.
   PubMed Web of Science ®Google Scholar
• Abbott NJ, Patabendige AA, Dolman DE, et al. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37:13–25.
   PubMed Web of Science ®Google Scholar
• Quaegebeur A, Lange C, Carmeliet P. (2011)The neurovascular link in health and disease: molecular mechanisms and therapeutic implications. Neuron. 2011;71:406–424.
   PubMed Web of Science ®Google Scholar
• Daood M, Tsai C, Ahdab-Barmada M, et al. ABC transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS. Neuropediatrics. 2008;39:211–218.
   PubMed Web of Science ®Google Scholar
• Ghersi-Egea JF, Gazzin S, Strazielle N. Blood-brain interfaces and bilirubin-induced neurological diseases. Cur Pharm Des. 2009;15:2893–2907.
   PubMed Web of Science ®Google Scholar
• Jones PM, George AM. The ABC transporter structure and mechanism: perspectives on recent research. Cell Mol Life Sci. 2004;61(6):682–699.
   PubMed Web of Science ®Google Scholar
• Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta. 1976;455:152–162.
   PubMed Web of Science ®Google Scholar
• Löscher W, Potschka H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci. 2005a;6(8):591–602.
   PubMed Web of Science ®Google Scholar
• Löscher W, Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx. 2005b;2(1):86–98.
   PubMedGoogle Scholar
• Bruhn O, Cascorbi I. Polymorphisms of the drug transporters ABCB1, ABCG2, ABCC2 and ABCC3 and their impact on drug bioavailability and clinical relevance. Expert Opin Drug Metab Toxicol. 2014;10(10):1337–1354.
   PubMed Web of Science ®Google Scholar
• Cheng J-W, Zhang L-J, Hou Y-Q, et al. Association between MDR1 C3435T polymorphism and refractory epilepsy in the Chinese population: a systematic review and meta-analysis. Epilepsy Behav. 2014;36:173–179.
   PubMed Web of Science ®Google Scholar
• Moons T, De Roo M, Claes S, et al. Relationship between P-glycoprotein and second-generation antipsychotics. Pharmacogenomics. 2011;12(8):1193–1211.
   PubMed Web of Science ®Google Scholar
• Rosenhagen MC, Uhr M. The clinical impact of ABCB1 polymorphisms on the treatment of psychiatric diseases. Curr Pharm Des. 2011;17(26):2843–2851.
   PubMed Web of Science ®Google Scholar
• Ashraf T, Kao A, Bendayan R. Functional expression of drug transporters in glial cells: potential role on drug delivery to the CNS. Adv Pharmacol. 2014;71:45–111.
   PubMedGoogle Scholar
• Chen J, Zhang X, Kusumo H, et al. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis. Biochim Biophys Acta. 2013;1831(2):263–275.
   PubMed Web of Science ®Google Scholar
• Sun Y, Luo X, Yang K, et al. Neural overexpression of multidrug resistance-associated protein 1 and refractory epilepsy: a meta-analysis of 9 studies. Int J Neurosci. 2015;22:1–26.
   Google Scholar
• Willyerd FA, Empey PE, Philbrick A, et al. Expression of ATP-binding cassette transporters B1 and C1 after severe traumatic brain injury in humans. J Neurotrauma. 2016;33(2):226–231.
   PubMed Web of Science ®Google Scholar
• Rama AR, Alvarez PJ, Madeddu R, et al. ABC transporters as differentiation markers in glioblastoma cells. Mol Biol Rep. 2014;41(8):4847–4851.
   PubMed Web of Science ®Google Scholar
• Miller DS, Graeff C, Droulle L, et al. Xenobiotic efflux pumps in isolated fish brain capillaries. Am J Physiol. 2002;282:R191–R198.
   Web of Science ®Google Scholar
• Bauer B, Hartz AM, Fricker G, et al. Modulation of p-glycoprotein transport function at the blood-brain barrier. Exp Biol Med (Maywood). 2005;230(2):118–127.
   PubMed Web of Science ®Google Scholar
• Bendayan R, Ronaldson PT, Gingras D, et al. In situ localization of P-glycoprotein (ABCB1) in human and rat brain. J Histochem Cytochem. 2006;54(10):1159–1167.
   PubMed Web of Science ®Google Scholar
• Soontornmalai A, Vlaming ML, Fritschy J-M. Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood-brain barrier. Neuroscience. 2006;138(1):159–169.
   PubMed Web of Science ®Google Scholar
• Nies AT, Jedlitschky G, König J, et al. Expression and immunolocalization of the multidrug resistance proteins, ABCC1-ABCC6 (ABCC1-ABCC6), in human brain. Neuroscience. 2004;129(2):349–360.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Schuetz JD, Elmquist WF, et al. Plasma membrane localization of multidrug resistance-associated protein homologs in brain capillary endothelial cells. J Pharmacol Exp Ther. 2004;311(2):449–455.
   PubMed Web of Science ®Google Scholar
• Roberts LM, Black DS, Raman C, et al. Subcellular localization of transporters along the rat blood-brain barrier and blood-cerebral-spinal fluid barrier by in vivo biotinylation. Neuroscience. 2008;155(2):423–438.
   PubMed Web of Science ®Google Scholar
• Gutmann H, Török M, Fricker G, et al. Modulation of ABCC expression in porcine brain capillary endothelial cells in vitro. Drug Metab Disp. 1999;27:937–941.
   PubMed Web of Science ®Google Scholar
• Gazzin S, Strazielle N, Schmitt C, et al. Differential expression of the multidrug resistance-related proteins ABCb1 and ABCc1 between blood-brain interfaces. J Comp Neurol. 2008;510(5):497–507.
   PubMed Web of Science ®Google Scholar
• Miller DS, Nobmann SN, Gutmann H, et al. Xenobiotic transport across isolated brain microvessels studied by confocal microscopy. Mol Pharm. 2000;58:1357–1367.
   PubMed Web of Science ®Google Scholar
• Fricker G, Nobmann S, Miller DS. Permeability of porcine blood brain barrier to somatostatin analogs. Brit J Pharmacol. 2002;135:1308–1314.
   PubMed Web of Science ®Google Scholar
• Potschka H, Fedrowitz M, Löscher W. Multidrug resistance protein ABCC2 contributes to blood brain barrier function and restricts antiepileptic drug activity. J Pharmacol Exp Ther. 2003;306:124–131.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Han H, Elmquist WF, et al. Expression of various multidrug resistance-associated protein (ABCC) homologues in brain microvessel endothelial cells. Brain Res. 2000;876:148–153.
   PubMed Web of Science ®Google Scholar
• Cooray HC, Blackmore CG, Maskell L, et al. Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport. 2002;13(16):2059–6.
   PubMed Web of Science ®Google Scholar
• Schinkel AH, Mayer U, Wagenaar E, et al. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci U S A. 1997;94:4028–4033.
   PubMed Web of Science ®Google Scholar
• Schinkel AH. P-glycoprotein, a gatekeeper in the blood–brain barrier. Adv Drug Deliv Rev. 1999;36:179–194.
   PubMed Web of Science ®Google Scholar
• Durmus S, Xu N, Sparidans RW, et al. P-glycoprotein (MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) restrict brain accumulation of the JAK1/2 inhibitor, CYT387. Pharmacol Res. 2013;76:9–16.
   PubMed Web of Science ®Google Scholar
• Kort A, Sparidans RW, Wagenaar E, et al. Brain accumulation of the EML4-ALK inhibitor ceritinib is restricted by P-glycoprotein (P-GP/ABCB1) and breast cancer resistance protein (BCRP/ABCG2). Pharmacol Res. 2015;102:200–207.
   PubMed Web of Science ®Google Scholar
• Fellner S, Bauer B, Miller DS, et al. Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J Clin Invest. 2002;110(9):1309–1318.
   PubMed Web of Science ®Google Scholar
• Hubensack M, Müller C, Höcherl P, et al. Effect of the ABCB1 modulators elacridar and tariquidar on the distribution of paclitaxel in nude mice. J Cancer Res Clin Oncol. 2008;134(5):597–607.
   PubMed Web of Science ®Google Scholar
• Tivnan A, Zakaria Z, O’Leary C, et al. Inhibition of multidrug resistance protein 1 (ABCC1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme. Front Neurosci. 2015;9:218.
   PubMed Web of Science ®Google Scholar
• Twentyman PR. Cyclosporins as drug resistance modifiers. Biochem Pharmacol. 1992;43(1):109–117.
   PubMed Web of Science ®Google Scholar
• Breedveld P, Pluim D, Cipriani G, et al. The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res. 2005;65(7):2577–2582.
   PubMed Web of Science ®Google Scholar
• Allen JD, van Loevezijn A, Lakhai JM, et al. Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther. 2002;1(6):417–425.
   PubMed Web of Science ®Google Scholar
• Kalvass JC, Polli JW, Bourdet DL, et al. International Transporter Consortium Why clinical modulation of efflux transport at the human blood-brain barrier is unlikely: the ITC evidence-based position. Clin Pharmacol Ther. 2013;94(1):80–94.
   PubMed Web of Science ®Google Scholar
• Bagal S, Bungay P. Restricting CNS penetration of drugs to minimise adverse events: role of drug transporters. Drug Discov Today Technol. 2014;12:e79–e85.
   PubMedGoogle Scholar
• Bauer B, Hartz A, Fricker G, et al. Pregnane X receptor up-regulation of p-glycoprotein expression and transport function p-glycoprotein at the blood brain barrier. Molec Pharmacol. 2004;66:413–419.
   PubMed Web of Science ®Google Scholar
• Narang VS, Fraga C, Kumar N, et al. Dexamethasone increases expression and activity of multidrug resistance transporters at the rat blood-brain barrier. Am J Physiol Cell Physiol. 2008;295(2):C440–50.
   PubMed Web of Science ®Google Scholar
• Bauer B, Yang X, Hartz AM, et al. In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation. Mol Pharmacol. 2006;70:1212–1219.
   PubMed Web of Science ®Google Scholar
• Wang X, Hawkins BT, Miller DS. Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. FASEB J. 2011;25(2):644–652.
   PubMed Web of Science ®Google Scholar
• Wang X, Sykes DB, Miller DS. Constitutive androstane receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. Mol Pharmacol. 2010;78(3):376–383.
   PubMed Web of Science ®Google Scholar
• Miller DS. Regulation of ABC transporters at the blood-brain barrier. Clin Pharmacol Ther. 2015;97(4):395–403.
   PubMed Web of Science ®Google Scholar
• Miller DS. Regulation of ABC transporters blood-brain barrier: the good, the bad, and the ugly. Adv Cancer Res. 2015;125:43–70.
   PubMed Web of Science ®Google Scholar
• Tome ME, Schaefer CP, Jacobs LM, et al. Identification of P-glycoprotein co-fractionating proteins and specific binding partners in rat brain microvessels. J Neurochem. 2015;134(2):200–210.
   PubMed Web of Science ®Google Scholar
• Mrozikiewicz PM, Bogacz A, Bartkowiak-Wieczorek J, et al. Screening for impact of popular herbs improving mental abilities on the transcriptional level of brain transporters. Acta Pharm. 2014;64(2):223–232.
   PubMed Web of Science ®Google Scholar
• Vogelgesang S, Cascorbi I, Schroeder E, et al. Deposition of Alzheimer’s beta-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans. Pharmacogenetics. 2002;12(7):535–541.
   PubMedGoogle Scholar
• Cirrito JR, Deane R, Fagan AM, et al. P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model. J Clin Invest. 2005;115(11):3285–3290.
   PubMed Web of Science ®Google Scholar
• Brenn A, Grube M, Jedlitschky G, et al. St. John’s Wort reduces beta-amyloid accumulation in a double transgenic Alzheimer’s disease mouse model-role of P-glycoprotein. Brain Pathol. 2014;24(1):18–24.
   PubMed Web of Science ®Google Scholar
• Seegers U, Potschka H, Löscher W. Transient increase of P-glycoprotein expression in endothelium and parenchyma of limbic brain regions in the kainate model of temporal lobe epilepsy. Epilepsy Res. 2002;51(3):257–268.
   PubMed Web of Science ®Google Scholar
• Bernhart E, Damm S, Wintersperger A, et al. Interference with distinct steps of sphingolipid synthesis and signaling attenuates proliferation of U87MG glioma cells. Biochem Pharmacol. 2015;96(2):119–130.
   PubMed Web of Science ®Google Scholar
• Liu J, Chi N, Zhang JY, et al. Isolation and characterization of cancer stem cells from medulloblastoma. Genet Mol Res. 2015;14:3355–3361.
   PubMed Web of Science ®Google Scholar
• Sane R, Wu S-P, Zhang R, et al. The effect of ABCG2 and ABCC4 on the pharmacokinetics of methotrexate in the brain. Drug Metab Dispos. 2014;42(4):537–540.
   PubMed Web of Science ®Google Scholar
• Porro A, Haber M, Diolaiti D, et al. Direct and coordinate regulation of ATP-binding cassette transporter genes by Myc factors generates specific transcription signatures that significantly affect the chemoresistance phenotype of cancer cells. J Biol Chem. 2010;285(25):19532–19543.
   PubMed Web of Science ®Google Scholar
• Spudich A, Kilic E, Xing H, et al. Inhibition of multidrug resistance transporter-1 facilitates neuroprotective therapies after focal cerebral ischemia. Nat Neurosci. 2006;9(4):487–488.
   PubMed Web of Science ®Google Scholar
• Kilic E, Spudich A, Kilic U, et al. ABCC1: a gateway for pharmacological compounds to the ischaemic brain. Brain. 2008;131(Pt 10):2679–2689.
   PubMed Web of Science ®Google Scholar
• ElAli A, Hermann DM. Apolipoprotein E controls ATP-binding cassette transporters in the ischemic brain. Sci Signal. 2010;3(142):ra72.
   PubMed Web of Science ®Google Scholar
• Riddell DR, Zhou H, Comery TA, et al. The LXR agonist TO901317 selectively lowers hippocampal Abeta42 and improves memory in the Tg2576 mouse model of Alzheimer’s disease. Mol Cell Neurosci. 2007;34(4):621–628.
   PubMed Web of Science ®Google Scholar
• Macé S, Cousin E, Ricard S, et al. ABCA2 is a strong genetic risk factor for early-onset Alzheimer’s disease. Neurobiol Dis. 2005;18(1):119–125.
   PubMed Web of Science ®Google Scholar
• Lam FC, Liu R, Lu P, et al. beta-Amyloid efflux mediated by p-glycoprotein. J Neurochem. 2001;76(4):1121–1128.
   PubMed Web of Science ®Google Scholar
• Kuhnke D, Jedlitschky G, Grube M, et al. MDR1-P-Glycoprotein (ABCB1) mediates transport of Alzheimer’s amyloid-beta peptides–implications for the mechanisms of abeta clearance at the blood-brain barrier. Brain Pathol. 2007;17(4):347–353.
   PubMed Web of Science ®Google Scholar
• Xiong H, Callaghan D, Jones A, et al. ABCG2 is upregulated in Alzheimer’s brain with cerebral amyloid angiopathy and may act as a gatekeeper at the blood-brain barrier for abeta(1-40) peptides. J Neurosci. 2009;29(17):5463–5475.
   PubMed Web of Science ®Google Scholar
• Nelson PT, Jicha GA, Wang WX, et al. ABCC9/SUR2 in the brain: implications for hippocampal sclerosis of aging and a potential therapeutic target. Ageing Res Rev. 2015;24:S1568–1637(15)30009–X.
   Web of Science ®Google Scholar
• Quazi F, Molday RS. Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants. J Biol Chem. 2013;288(48):34414–34426.
   PubMed Web of Science ®Google Scholar
• Mosser J, Douar AM, Sarde CO, et al. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature. 1993;361(6414):726–730.
   PubMed Web of Science ®Google Scholar
• Kooij G, Kroon J, Paul D, et al. P-glycoprotein regulates trafficking of CD8(+) T cells to the brain parenchyma. Acta Neuropathol. 2014;127(5):699–711.
   PubMed Web of Science ®Google Scholar
• Kooij G, Van Horssen J, Bandaru V, et al. Role of ATP-binding cassette transporters in neuro-inflammation: relevance for bioactive lipids. Front Pharmacol. 2012;30(3):74.
   Google Scholar
• Gray E, Rice C, Hares K, et al. Reductions in neuronal peroxisomes in multiple sclerosis grey matter. Mult Scler. 2014;20(6):651–659.
   PubMed Web of Science ®Google Scholar
• García-Carrasco M, Mendoza-Pinto C, Macias Díaz S, et al. P-glycoprotein in autoimmune rheumatic diseases. Autoimmun Rev. 2015;14(7):594–600.
   PubMed Web of Science ®Google Scholar
• Rapposelli S, Digiacomo M, Balsamo A. P-GP transporter and its role in neurodegenerative diseases. Curr Top Med Chem. 2009;9(2):209–217.
   PubMed Web of Science ®Google Scholar
• Liu Q, Hou J, Chen X, et al. P-glycoprotein mediated efflux limits the transport of the novel anti-Parkinson’s disease candidate drug FLZ across the physiological and PD pathological in vitro BBB models. PLoS One. 2014;9(7):e102442.
   PubMed Web of Science ®Google Scholar
• Jablonski MR, Jacob DA, Campos C, et al. Selective increase of two ABC drug efflux transporters at the blood-spinal cord barrier suggests induced pharmacoresistance in ALS. Neurobiol Dis. 2012;47(2):194–200.
   PubMed Web of Science ®Google Scholar
• Milane A, Fernandez C, Dupuis L, et al. P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis. Neurosci Lett. 2010;472(3):166–170.
   PubMed Web of Science ®Google Scholar
• Scheen L, Patton G, Fares H. Suppression of the cup-5 mucolipidosis type IV-related lysosomal dysfunction by the inactivation of an ABC transporter in C. elegans. Development. 2006;133(19):3939–4.
   PubMed Web of Science ®Google Scholar
• Robillard KR, Hoque MT, Bendayan R. Expression of ATP-binding cassette membrane transporters in a HIV-1 transgenic rat model. Biochem Biophys Res Commun. 2014;444(4):531–536.
   PubMed Web of Science ®Google Scholar
• Potschka H. Role of CNS efflux drug transporters in antiepileptic drug delivery: overcoming CNS efflux drug transport. Adv Drug Deliv Rev. 2012;64(10):943–952.
   PubMed Web of Science ®Google Scholar
• Ma A, Wang C, Chen Y, et al. P-glycoprotein alters blood-brain barrier penetration of antiepileptic drugs in rats with medically intractable epilepsy. Drug Des Devel Ther. 2013;7:1447–1454.
   PubMed Web of Science ®Google Scholar
• Luna-Munguia H, Salvamoser JD, Pascher B, et al. Glutamate-mediated upregulation of the multidrug resistance protein 2 in porcine and human brain capillaries. J Pharmacol Exp Ther. 2015;352(2):368–378.
   PubMed Web of Science ®Google Scholar
• Bauer B, Hartz AM, Pekcec A, et al. Seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier through glutamate and cyclooxygenase-2 signaling. Mol Pharmacol. 2008;73(5):1444–1453.
   PubMed Web of Science ®Google Scholar
• Bankstahl JP, Hoffmann K, Bethmann K, et al. Glutamate is critically involved in seizure-induced overexpression of P-glycoprotein in the brain. Neuropharmacology. 2008;54(6):1006–1016.
   PubMed Web of Science ®Google Scholar
• McCaffrey G, Staatz WD, Sanchez-Covarrubias L, et al. P-glycoprotein trafficking at the blood-brain barrier altered by peripheral inflammatory hyperalgesia. J Neurochem. 2012;122:962–975.
   PubMed Web of Science ®Google Scholar
• Davis TP, Sanchez-Covarubias L, Tome ME. P-glycoprotein trafficking as a therapeutic target to optimize CNS drug delivery. Adv Pharmacol. 2014;71:25–44.
   PubMedGoogle Scholar
• Liu L, Liu XD. Alterations in function and expression of ABC transporters at blood-brain barrier under diabetes and the clinical significances. Front Pharmacol. 2014;10(5):273.
   Google Scholar
• Alves MG, Oliveira PF, Socorro S, et al. Impact of diabetes in blood-testis and blood-brain barriers: resemblances and differences. Curr Diabetes Rev. 2012;8:401–412.
   PubMedGoogle Scholar
• Liu H, Xu X, Yang Z, et al. Impaired function and expression of P-glycoprotein in blood-brain barrier of streptozotocin-induced diabetic rats. Brain Res. 2006;1123(1):245–252.
   PubMed Web of Science ®Google Scholar
• Liu YC, Liu HY, Yang HW, et al. Impaired expression and function of breast cancer resistance protein (Bcrp) in brain cortex of streptozocin-induced diabetic rats. Biochem Pharmacol. 2007;74:1766–1772.
   PubMed Web of Science ®Google Scholar
• Zhang LL, Lu L, Jin S, et al. Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats. Acta Pharmacol Sin. 2012;32:956–966.
   Web of Science ®Google Scholar
• Wu K-C, Pan H-J, Yin H-S, et al. Change in P-glycoprotein and caveolin protein expression in brain striatum capillaries in New Zealand obese mice with type 2 diabetes. Life Sci. 2009;85(23–26):775–781.
   PubMed Web of Science ®Google Scholar
• Reichel V, Burghard S, John I, et al. P-glycoprotein and breast cancer resistance protein expression and function at the blood-brain barrier and blood-cerebrospinal fluid barrier (choroid plexus) in streptozotocin-induced diabetes in rats. Brain Res. 2011;1370:238–245.
   PubMed Web of Science ®Google Scholar
• Liu H, Liu X, Jia L, et al. Insulin therapy restores impaired function and expression of P-glycoprotein in blood-brain barrier of experimental diabetes. Biochem Pharmacol. 2008;75:1649–1658.
   PubMed Web of Science ®Google Scholar
• Liu H, Yang H, Wang D, et al. Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-kappaB pathway but not a PI3K/Akt pathway. Eur J Pharmacol. 2009;602:277–282.
   Web of Science ®Google Scholar