Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-κB pathway but not a PI3K/Akt pathway

Liu, Haiyan; Yang, Huiwen; Wang, Dianlei; Liu, Yuchun; Liu, Xiaodong; Li, Yang; Xie, Lin; Wang, Guangji

doi:10.1016/j.ejphar.2008.11.026

Cited by 33 publications

(18 citation statements)

References 36 publications

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“…Therefore, we consider that recovery of P-gp expression by AG is unlikely to be due to its anti-glycation effect. Interestingly, since it has been reported that P-gp expression is maintained by serum insulin through PKC/NF-kappa B signaling (Liu et al 2009), we cannot deny the possibility that insulin deficiency contributed to the decrease of P-gp expression, although it remains to be determined.…”

Section: Groupmentioning

confidence: 95%

Inducible nitric oxide synthase-mediated decrease of intestinal P-glycoprotein expression under streptozotocin-induced diabetic conditions

2010

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Section: Groupmentioning

confidence: 95%

Inducible nitric oxide synthase-mediated decrease of intestinal P-glycoprotein expression under streptozotocin-induced diabetic conditions

2010

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“…In addition to their common function as a drug efflux transporter, the Abcb1 isoforms appear to have their own specific function: Abcb1a was reported to regulate cell volume by influencing swelling activated chloride currents via a protein kinase C sensitive phosphorylation site on P-GP [27] , while Abcb1b has been shown to be involved in apoptosis [28] and cellular stress [29,30] . However, these views remain controversial [31,32] . The expression levels of P-GP protein in the indicated tissues were measured by Western blot.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats

et al. 2011

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Aim: To investigate the changes of expression and function of P-glycoprotein (P-GP) in cerebral cortex, hippocampus, liver, intestinal mucosa and kidney of streptozocin-induced diabetic rats. Methods: Diabetic rats were prepared via a single dose of streptozocin (65 mg/kg, ip). Abcb1/P-GP mRNA and protein expression levels in tissues were evaluated using quantitative real time polymerase chain reaction (QRT-PCR) analysis and Western blot, respectively. P-GP function was investigated via measuring tissue-to-plasma concentration ratios and body fluid excretion percentages of rhodamine 123. Results: In 5-and 8-week diabetic rats, Abcb1a mRNA levels were significantly decreased in cerebral cortices and intestinal mucosa, but dramatically increased in hippocampus and kidney. In liver, the level was increased in 5-week diabetic rats, and decreased in 8-week diabetic rats. Abcb1b mRNA levels were increased in cerebral cortex, hippocampus and kidney, but reduced in liver and intestinal mucosa in the diabetic rats. Western blot results were in accordance with the alterations of Abcb1a mRNA levels in most tissues examined. P-GP activity was markedly decreased in most tissues of diabetic rats, except kidney tissues. Conclusion: Alterations in the expression and function of Abcb1/P-GP under diabetic conditions are tissue specific, Abcb1 specific and diabetic duration-dependent.

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“…Insulin enhances transport of the amino acids tyrosine and tryptophan (Cangiano, et al, 1983; Daniel, Love, Moorhouse, & Pratt, 1981; Tagliamonte, DeMontis, Olianas, Onali, & Gessa, 1976), increases the blood-to-brain transport of leptin (Kastin & Akerstrom, 2001), increases expression and function of the efflux transporter P-glycoprotein, but decreases expression and function of another efflux transporter, breast cancer resistance protein (H. Liu, Yang, Wang, Liu, Li, et al, 2009; X.…”

Section: Effects Of Insulin On Becs and Bbb Functionmentioning

confidence: 99%

Insulin in the brain: There and back again

Banks

Owen

Erickson

2012

Pharmacology & Therapeutics

481

380

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Insulin performs unique functions within the CNS. Produced nearly exclusively by the pancreas, insulin crosses the blood-brain barrier (BBB) using a saturable transporter, affecting feeding and cognition through CNS mechanisms largely independent of glucose utilization. Whereas peripheral insulin acts primarily as a metabolic regulatory hormone, CNS insulin has an array of effects on brain that may more closely resemble the actions of the ancestral insulin molecule. Brain endothelial cells (BEC), the cells that form the vascular BBB and contain the transporter that translocates insulin from blood to brain, is itself regulated by insulin. The insulin transporter is altered by physiological and pathological factors including hyperglycemia and the diabetic state. The latter can lead to BBB disruption. Pericytes, pluripotent cells in intimate contact with the BEC, protect the integrity of the BBB and its ability to transport insulin. Most of insulin’s known actions within the CNS are mediated through two canonical pathways, the phosphoinositide-3 kinase (PI3)/Akt and Ras/mitogen activated kinase (MAPK) cascades. Resistance to insulin action within the CNS, sometimes referred to as diabetes mellitus type III, is associated with peripheral insulin resistance, but it is possible that variable hormonal resistance syndromes exist so that resistance at one tissue bed may be independent of that at others. CNS insulin resistance is associated with Alzheimer’s disease, depression, and impaired baroreceptor gain in pregnancy. These aspects of CNS insulin action and the control of its entry by the BBB are likely only a small part of the story of insulin within the brain.

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Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-κB pathway but not a PI3K/Akt pathway

Cited by 33 publications

References 36 publications

Inducible nitric oxide synthase-mediated decrease of intestinal P-glycoprotein expression under streptozotocin-induced diabetic conditions

Inducible nitric oxide synthase-mediated decrease of intestinal P-glycoprotein expression under streptozotocin-induced diabetic conditions

Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats

Insulin in the brain: There and back again

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