Insulin expression in cultured astrocytes and the decrease by amyloid β

[en] Insulin resistance in brain has been reported in Alzheimer's diseases (AD). Insulin signaling is important for homeostasis in brain function and reported to be disturbed in neurons leading to tau phosphorylation and neurofibrillary tangles. Many investigations of insulin in neurons have been reported; however, it has not been reported whether astrocytes also produce insulin. In the present study, we assessed the expression of insulin in astrocytes cultured from rat embryonic brain and the effects of amyloid β1-42 (Aβ) and lipopolysaccharide (LPS) on the expression. We found that astrocytes expressed preproinsulin mRNAs and insulin protein, and that Aβ or LPS decreased these expressions. Antioxidants, glutathione and N-acetylcysteine, restored the decreases in insulin mRNA expression by Aβ and by LPS. Insulin protein was detected in astrocyte conditioned medium. These results suggest that astrocytes express and secrete insulin. Oxidative stress might be involved in the decreased insulin expression by Aβ or LPS. The insulin decrease by Aβ in astrocytes could be a novel disturbing mechanism for brain insulin signaling in AD.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Takano, Katsura

Koarashi, Keisuke

Kawabe, Kenji

ITAKURA, Masanori ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group

Nakajima, Hidemitsu

Moriyama, Mitsuaki

Nakamura, Yoichi

External co-authors :

yes

Language :

English

Title :

Insulin expression in cultured astrocytes and the decrease by amyloid β

Publication date :

2018

Journal title :

Neurochemistry International

ISSN :

0197-0186

Publisher :

Elsevier, Nl

Volume :

119

Issue :

Eur. J. Pharmacol. 490 1–3 2004

Pages :

171-177

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://app.readcube.com/library/a9ec3f18-47dd-4e50-bc89-1e8528daa3d7/item/9903e228-cd3f-4522-a92a-8877c8537f11

Available on ORBilu :

since 29 November 2023

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Bibliography

Banks, W.A., The source of cerebral insulin. Eur. J. Pharmacol. 490:1–3 (2004), 5–12.
Bedse, G., Di Domenico, F., Serviddio, G., Cassano, T., Abberant insulin signaling in Alzheimer's disease: current knowledge. Front. Neurosci., 9, 2015, 10.3389/fnins.2015.00204 Article 204.
Chang-Chen, K.J., Mullur, R., Bernal-Mizrachi, E., β-cell failure as a complication of diabetes. Rev. Endocr. Metab. Disord. 9 (2008), 329–343.
Clarke, D.W., Mudd, L., Boyd, F.T. Jr., Fields, M., Raizada, M.K., Insulin is released from rat brain neuronal cells in culture. J. Neurochem. 47 (1986), 831–836.
Craft, S., Peskind, E., Schwartz, W., Gerard, D., Raskind, M., Porte, D. Jr., Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease. Neurology 50:1 (1998), 164–168.
Dickson, B., Wiring the brain with insulin. Science 300:5618 (2003), 440–441.
Dorfman, V.B., Pasquini, L., Riudavets, M., López-Costa, J.J., Villegas, A., Lopera, F., Troncoso, J.C., Castaño, E.M., Morelli, L., Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer's disease. Neurobiol. Aging 31 (2010), 1743–1757.
Faizi, M., Seydi, E., Abarghuyi, S., Salimi, A., Nasoohi, S., Pourahmad, J., A search for mitochondrial damage in Alzheimer's disease using isolated rat brain mitochondria. Iran. J. Pharm. Res. 15 (2016), 185–195.
García-Cáceres, C., Quarta, C., Varela, L., Gao, Y., Gruber, T., Legutko, B., Jastroch, M., Johansson, P., Ninkovic, J., Yi, C.X., Le Thuc, O., Szigeti-Buck, K., Cai, W., Meyer, C.W., Pfluger, P.T., Fernandez, A.M., Luquet, S., Woods, S.C., Torres-Alemán, I., Kahn, C.R., Götz, M., Horvath, T.L., Tschöp, M.H., Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell 166 (2016), 867–880.
Glass, C.K., Saijo, K., Winner, B., Marchetto, M.C., Gage, F.H., Mechanisms underlying inflammation in neurodegeneration. Cell 140 (2010), 918–934.
Havrankova, J., Roth, J., Brownstein, M., Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272:5656 (1978), 827–829.
Havrankova, J., Roth, J., Brownstein, M.J., Concentrations of insulin and of insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents. J. Clin. Invest 64:2 (1979), 636–642.
Havrankova, J., Schmechel, D., Roth, J., Brownstein, M., Identification of insulin in rat brain. Proc. Natl. Acad. Sci. U. S. A. 75 (1978), 5737–5741.
Huang, N.Q., Jin, H., Zhou, S., Shi, J., Jin, F., TLR4 is a link between diabetes and Alzheimer's disease. Behav. Brain Res. 316 (2017), 234–244.
Itakura, M., Nakajima, H., Kubo, T., Semi, Y., Kume, S., Higashida, S., Kaneshige, A., Kuwamura, M., Harada, N., Kita, A., Azuma, Y.T., Yamaji, R., Inui, T., Takeuchi, T., Glyceraldehyde-3-phosphate dehydrogenase aggregates accelerate amyloid-β amyloidogenesis in Alzheimer disease. J. Biol. Chem. 290:43 (2015), 26072–26087.
Kandimalla, R., Thirumala, V., Reddy, P.H., Is Alzheimer's disease a type 3 diabetes? A critical appraisal. Biochim. Biophys. Acta 1863:5 (2016), 1078–1089.
Kremerskothen, J., Wendholt, D., Teber, I., Barnekow, A., Insulin-induced expression of the activity-regulated cytoskeleton-associated gene (ARC) in human neuroblastoma cells requires p21ras, mitogen-activated protein kinase/extracellular regulated kinase and src tyrosine kinases but is protein kinase C-independent. Neurosci. Lett. 321:3 (2002), 153–156.
Laron, Z., Insulin and the brain. Arch. Physiol. Biochem. 115:2 (2009), 112–116.
Li, H., Liu, B., Huang, J., Chen, H., Guo, X., Yuan, Z., Insulin inhibits lipopolysaccharide-induced nitric oxide synthase expression in rat primary astrocytes. Brain Res. 1506 (2013), 1–11.
Liu, Y., Liu, F., Grundke, I., Iqbal, K., Gong, C., Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes. Pathology 225 (2011), 54–62.
McNay, E.C., Ong, C.T., McCrimmon, R.J., Cresswell, J., Bogan, J.S., Sherwin, R.S., Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol. Learn Mem. 93:4 (2010), 546–553.
Nemoto, T., Toyoshima-Aoyama, F., Yanagita, T., Maruta, T., Fujita, H., Koshida, T., Yonaha, T., Wada, A., Sawaguchi, A., Murakami, M., New insights concerning insulin synthesis and its secretion in rat hippocampus and cerebral cortex: amyloid β1-42-induced reduction of proinsulin level via glycogen synthase kinase-3β. Cell. Signal. 26 (2013), 253–259.
Obici, S., Zhang, B.B., Karkanias, G., Rossetti, L., Hypothalamic insulin signaling is required for inhibition of glucose production. Nat. Med. 8 (2002), 1376–1382.
Pugazhenthi, S., Qin, L., Reddy, P.H., Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease. Biochim. Biophys. Acta 1863:5 (2016), 1037–1045.
Sawada, M., Kondo, N., Suzumura, A., Marunouchi, T., Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Res. 491 (1989), 394–397.
Schechter, R., Beju, D., Gaffney, T., Schaefer, F., Whetsell, L., Preproinsulin I and II mRNAs and insulin electron microscopic immunoreaction are present within the rat fetal nervous system. Brain Res. 736:1–2 (1996), 16–27.
Schechter, R., Whitmire, J., Holtzclaw, L., George, M., Harlow, R., Devaskar, S.U., Developmental regulation of insulin in the mammalian central nervous system. Brain Res. 582:1 (1992), 27–37.
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P.H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., O'Gorman, J., Qian, F., Arastu, M., Li, M., Chollate, S., Brennan, M.S., Quintero-Monzon, O., Scannevin, R.H., Arnold, H.M., Engber, T., Rhodes, K., Ferrero, J., Hang, Y., Mikulskis, A., Grimm, J., Hock, C., Nitsch, R.M., Sandrock, A., The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature 537:7618 (2016), 50–56.
Song, J., Wu, L., Chen, Z., Kohanski, R.A., Pick, L., Axons guided by insulin receptor in Drosophila visual system. Science 300:5618 (2003), 502–505.
Takano, K., Sugita, K., Moriyama, M., Hashida, K., Hibino, S., Choshi, T., Murakami, R., Yamada, M., Suzuki, H., Hori, O., Nakamura, Y., A dibenzoylmethane derivative protects against hydrogen peroxide-induced cell death and inhibits lipopolysaccharide-induced nitric oxide production in cultured rat astrocytes. J. Neurosci. Res. 89 (2011), 955–965.
Tokutake, T., Kasuga, K., Yajima, R., Sekine, Y., Tezuka, T., Nishizawa, M., Ikeuchi, T., Hyperphosphorylation of Tau induced by naturally secreted amyloid-β at nanomolar concentrations is modulated by insulin-dependent Akt-GSK3β signaling pathway. J. Biol. Chem. 287:42 (2012), 35222–35233.
Unger, J.W., Livingston, J.N., Moss, A.M., Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. Prog. Neurobiol. 36 (1991), 343–362.
Vogt, M.C., Paeger, L., Hess, S., Steculorum, S.M., Awazawa, M., Hampel, B., Neupert, S., Nicholls, H.T., Mauer, J., Hausen, A.C., Predel, R., Kloppenburg, P., Horvath, T.L., Brüning, J.C., Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding. Cell 156:3 (2014), 495–509.
Wei, X., Ke, B., Zhao, Z., Ye, X., Gao, Z., Ye, J., Regulation of insulin degrading enzyme activity by obesity-associated factors and pioglitazone in liver of diet-induced obese mice. PLoS One, 9(4), 2014, e95399.
Zhao, W., Chen, H., Xu, H., Xu, H., Moore, E., Meiri, N., Quon, M.J., Alkon, D.L., Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats. J. Biol. Chem. 274:49 (1999), 34893–34902.
Zhao, W.Q., Fernanda, G., Sara, F., Chen, H., Lambert, M.P., Quon, M.J., Krafft, G.A., Klein, W.L., Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB J. 22 (2008), 246–260.