Top

Published in:

01-09-2011 | Original Paper

Influence of insulin on glutamine synthetase in the Müller glial cells of retina

Authors: Mohammad Shamsul Ola, Ken-ichi Hosoya, Kathryn F. LaNoue

Published in: Metabolic Brain Disease | Issue 3/2011

Abstract

Glutamine synthetase (GS), a Müller cell specific enzyme in the retina, is the key enzyme involve in glutamate metabolism. The goal of this study was to investigate the expression and regulation of GS by insulin in the cultured rat retinal Müller cells. Immunocytochemical and immunoblotting experiments showed that the cultured Müller cells express GS protein under normal cell culture conditions. Insulin treatments decreased the GS expression both in a time and dose dependent manner. Insulin also decreased the hydrocortisone induced GS expression. Furthermore, we investigated the expression and regulation of two other Müller cell specific enzymes known to be involved in glutamate metabolism, the mitochondrial branched chain aminotransferase (BCATm) and pyruvate carboxylase (PC). Immunoblotting experiments showed that Müller cells expressed both BCATm and PC. Treatments of cells with hydrocortisone or insulin did not influence the BCATm expression level. Hydrocortisone treatment of cells increased the PC expression but this induced expression was suppressed by insulin treatment. Müller cells expressed insulin receptor proteins (IRβ and IRS-1) and insulin activation induced the phosphotyrosine level of insulin receptor proteins. Moreover, hydrocortisone did not influence the expression or activation of these receptor proteins. The data suggests that insulin modulates the GS synthesis and may influence glutamate metabolism in the cultured retinal Müller cells but not by influencing the insulin signaling pathway.

Adamo M, Raizada MK, LeRoith D (1989) Insulin and insulin-like growth factor receptors in the nervous system. Mol Neurobiol 3:71–100PubMedCrossRef

Aizenman Y, de Vellis J (1987) Synergistic action of thyroid hormone, insulin and hydrocortisone on astrocyte differentiation. Brain Res 414:301–308PubMedCrossRef

Albrecht J, Wróblewska B, Mossakowski MJ (1982) The binding of insulin to cerebral capillaries and astrocytes of the rat. Neurochem Res 7:489–494PubMedCrossRef

Ambati J, Chalam KV, Chawla DK, D’Angio CT, Guillet EG, Rose SJ, Vanderlinde RE, Ambati BK (1997) Elevated gamma-aminobutyric acid, glutamate, and vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy. Arch Ophthalmol 115:1161–1166PubMed

Banks WA, Jaspan JB, Huang W, Kastin AJ (1997) Transport of insulin across the blood-brain barrier: saturability at euglycemic doses of insulin. Peptides 18:1423–1429PubMedCrossRef

Bhandari B, Miller RE (1987) Glutamine synthetase gene transcription in cultured 3 T3-L1 adipocytes: regulation by dexamethasone, insulin and dibutyryl cyclic AMP. Mol Cell Endocrinol 51:7–11PubMedCrossRef

Bringmann A, Pannicke T, Biedermann B, Francke M, Iandiev I, Grosche J, Wiedemann P, Albrecht J, Reichenbach A (2009) Role of retinal glial cells in neurotransmitter uptake and metabolism. Neurochem Int 54:143–160PubMedCrossRef

Bröer S, Brookes N (2001) Transfer of glutamine between astrocytes and neurons. J Neurochem 77(3):705–719PubMedCrossRef

Bui BV, Hu RG, Acosta ML, Donaldson P, Vingrys AJ, Kalloniatis M (2009) Glutamate metabolic pathways and retinal function. J Neurochem 111:589–599PubMedCrossRef

Chen CT, Alyahya K, Gionfriddo JR, Dubielzig RR, Madl JE (2008) Loss of glutamine synthetase immunoreactivity from the retina in canine primary glaucoma. Vet Ophthalmol 11:150–157PubMedCrossRef

Clarke DW, Mudd L, Boyd FT Jr, Fields M, Raizada MK (1986) Insulin is released from rat brain neuronal cells in culture. J Neurochem 47:831–836PubMedCrossRef

Fischer AJ, McGuire CR, Dierks BD, Reh TA (2002) Insulin and fibroblast growth factor 2 activate a neurogenic program in Müller glia of the chicken retina. J Neurosci 22:9387–9398PubMed

Ginsburg A, Stadtman ER (1973) In: Prusiner S, Stadtman ER (eds) The enzymes of glutamine metabolism. Academic, New York, pp 9–43

Gupta G, Azam M, Baquer NZ (1992) Modulation of rat brain insulin receptor kinase activity in diabetes. Neurochem Int 20:487–492PubMedCrossRef

Hamai M, Minokoshi Y, Shimazu T (1999) L-Glutamate and insulin enhance glycogen synthesis in cultured astrocytes from the rat brain through different intracellular mechanisms. J Neurochem 73:400–407PubMedCrossRef

Harada T, Harada C, Nakamura K, Quah HM, Okumura A, Namekata K, Saeki T, Aihara M, Yoshida H, Mitani A, Tanaka K (2007) The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma. J Clin Invest 117:1763–1770PubMedCrossRef

Hosoya K, Nakamura G, Akanuma S, Tomi M, Tachikawa M (2008) Dehydroascorbic acid uptake and intracellular ascorbic acid accumulation in cultured Müller glial cells (TR-MUL). Neurochem Int 52:1351–1357PubMedCrossRef

Hutson SM, Sweatt AJ, Lanoue KF (2005) Branched-chain [corrected] amino acid metabolism: implications for establishing safe intakes. J Nutr 135:1557S–1564SPubMed

Hyndman AG (1993) Identification of a population of amacrine cells rich in insulin receptors. Brain Res Dev Brain Res 75:289–292PubMedCrossRef

Juurlink BH, Schousboe A, Jørgensen OS, Hertz L (1981) Induction by hydrocortisone of glutamine synthetase in mouse primary astrocyte cultures. J Neurochem 36:136–142PubMedCrossRef

Khelil M, Rolland B, Fages C, Tardy M (1990) Glutamine synthetase modulation in astrocyte cultures of different mouse brain areas. Glia 3:75–80PubMedCrossRef

Kimura K, Kanda F, Okuda S, Chihara K (2001) Insulin-like growth factor 1 inhibits glucocorticoid-induced glutamine synthetase activity in cultured L6 rat skeletal muscle cells. Neurosci Lett 302:154–156PubMedCrossRef

LaNoue K, Carson V, Berkich DA, Hutson SM (2007) Mitochondrial/cytosolic interactions via metabolite shuttles and transporters. In: Handbook of neurochemistry and molecular neurobiology, 3 rd edn. pp. 589–616 Springer, Heidelberg

Li Q, Puro DG (2002) Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells. Invest Ophthalmol Vis Sci 43:3109–3116PubMed

Lieth E, Barber AJ, Xu B, Dice C, Ratz MJ, Tanase D, Strother JM (1998) Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group. Diabetes 47:815–820PubMedCrossRef

Lieth E, LaNoue KF, Antonetti DA, Ratz M (2000) Diabetes reduces glutamate oxidation and glutamine synthesis in the retina. The Penn State Retina Research Group. Exp Eye Res 70:723–730PubMedCrossRef

Lu MJ, Pulido JS, McCannel CA, Pulido JE, Hatfield RM, Dundervill RF 3rd, Shippy SA (2007) Detection of elevated signaling amino acids in human diabetic vitreous by rapid capillary electrophoresis. Exp Diab Res 2007:39765

Massagué J, Czech MP (1982) The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem 257:5038–5045PubMed

Michaelis EK (1998) Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog Neurobiol 54:369–415PubMedCrossRef

Miller RE, Pope SR, DeWille JW, Burns DM (1983) Insulin decreases and hydrocortisone increases the synthesis of glutamine synthetase in cultured 3 T3-L1 adipocytes. J Biol Chem 258:5405–5413PubMed

Moscona AA (1975) Hydrocortisone-mediated regulation of gene expression in embryonic neural retina: induction of glutamine synthetase. J Steroid Biochem 6:633–638PubMedCrossRef

Nakashima T, Tomi M, Tachikawa M, Watanabe M, Terasaki T, Hosoya K (2005) Evidence for creatine biosynthesis in Müller glia. Glia 52:47–52PubMedCrossRef

Rauen T, Wiessner M (2000) Fine tuning of glutamate uptake and degradation in glial cells: common transcriptional regulation of GLAST1 and GS. Neurochem Int 37:179–189PubMedCrossRef

Reiter CE, Sandirasegarane L, Wolpert EB, Klinger M, Simpson IA, Barber AJ, Antonetti DA, Kester M, Gardner TW (2003) Characterization of insulin signaling in rat retina in vivo and ex vivo. Am J Physiol Endocrinol Metab 285:E763–E774PubMed

Robinson SR (2000) Neuronal expression of glutamine synthetase in Alzheimer’s disease indicates a profound impairment of metabolic interactions with astrocytes. Neurochem Int 36:471–482PubMedCrossRef

Rodrigues M, Waldbillig RJ, Rajagopalan S, Hackett J, LeRoith D, Chader GJ (1988) Retinal insulin receptors: localization using a polyclonal anti-insulin receptor antibody. Brain Res 443:389–394PubMedCrossRef

Saini K, Thomas P, Bhandari B (1990) Hormonal regulation of stability of glutamine synthetase mRNA in cultured 3 T3-L1 adipocytes. Biochem J 267:241–244PubMed

Shaked I, Ben-Dror I, Vardimon L (2002) Glutamine synthetase enhances the clearance of extracellular glutamate by the neural retina. J Neurochem 83:574–580PubMedCrossRef

Tholey G, Sena AH, Ledig M (1986) Specific insulin-mediated regulation of glutamine synthetase in cultured chick astroglial cells. J Neurochem 47:1490–1492PubMedCrossRef

Tomi M, Funaki T, Abukawa H, Katayama K, Kondo T, Ohtsuki S, Ueda M, Obinata M, Terasaki T, Hosoya K (2003) Expression and regulation of L-cystine transporter, system xc-, in the newly developed rat retinal Müller cell line (TR-MUL). Glia 43:208–217PubMedCrossRef

Wang Y, Watford M (2007) Glutamine, insulin and glucocorticoids regulate glutamine synthetase expression in C2C12 myotubes, Hep G2 hepatoma cells and 3 T3 L1 adipocytes. Biochim Biophys Acta 1770:594–600PubMed

Ward MM, Jobling AI, Kalloniatis M, Fletcher EL (2005) Glutamate uptake in retinal glial cells during diabetes. Diabetologia 48:351–360PubMedCrossRef

Wei LT, Matsumoto H, Rhoads DE (1990) Release of immunoreactive insulin from rat brain synaptosomes under depolarizing conditions. J Neurochem 54:1661–1665PubMedCrossRef

Yu XH, Zhang H, Wang YH, Liu LJ, Teng Y, Liu P (2009) Time-dependent reduction of glutamine synthetase in retina of diabetic rats. Exp Eye Res 89:967–971PubMedCrossRef

Zou J, Wang YX, Dou FF, Lü HZ, Ma ZW, Lu PH, Xu XM (2010) Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons. Neurochem Int 56:577–584PubMedCrossRef

Title: Influence of insulin on glutamine synthetase in the Müller glial cells of retina
Authors: Mohammad Shamsul Ola
Ken-ichi Hosoya
Kathryn F. LaNoue
Publication date: 01-09-2011
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 3/2011
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-011-9245-y

At a glance: The STEP trials

Springer Medicine

Influence of insulin on glutamine synthetase in the Müller glial cells of retina

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2011

Absence of neuropsychological impairment in hyperammonaemia in healthy young adults; possible synergism in development of hepatic encephalopathy (HE) symptoms?

Effects of oxcarbazepine on monoamines content in hippocampus and head and body shakes and sleep patterns in kainic acid-treated rats

Peripheral immune challenge with viral mimic during early postnatal period robustly enhances anxiety-like behavior in young adult rats

A high cholesterol diet given to apolipoprotein E-knockout mice has a differential effect on the various neurotrophin systems in the hippocampus

Folate supplementation, MTHFR gene polymorphism and neural tube defects: a community based case control study in North India

Multi-dimensional MR spectroscopy: towards a better understanding of hepatic encephalopathy