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Effects of Glucose, Insulin, and Supernatant from Pancreatic β-cells on Brain–Pancreas Relative Protein in Rat Hippocampus

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Abstract

Brain–pancreas relative protein (BPRP) is a novel protein that mainly expresses in brain and pancreas. In our previous study, we found that various stressors significantly decreased the expression of BPRP in pancreas in vivo, accompanied by changes in insulin and glucose levels, and that expression of BPRP in pancreas also decreased significantly in diabetic rats induced by Streptozocin (STZ). All these findings suggest that BPRP may be a glucose or insulin-sensitive protein. However, how the changes in insulin or glucose levels influence the expression of BPRP in hippocampus requires further study. Here, we investigated the effects of insulin or glucose on the expression of BPRP in primary cultured hippocampal neurons. We supplied hippocampal neurons with glucose, insulin, or supernatant from pancreatic β-cells, which secrete insulin into the supernatant. Our data showed that insulin had beneficial effect on the viability while no significant effect on the expression of BPRP in hippocampal neurons. On the contrary, 40 mM glucose or free glucose culture significantly decreased the expression of BPRP, while had no significant effect on the viability and apoptosis of hippocampal neurons. Further study showed that levels of insulin in the supernatant collected from pancreatic β-cells medium changed over days, and that supernatant increased the viability of hippocampal neurons, while it had no obvious effect on the expression of BPRP in hippocampal neurons. These results suggest that BPRP may be a glucose-sensitive protein.

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References

  1. Yao XH, Yu HM, Koide SS, Li XJ (2003) Identification of a key protein associated with cerebral ischemia. Brain Res 967:11–18

    Article  PubMed  CAS  Google Scholar 

  2. Lin YH, Liu AH, Xu Y, Tie L, Yu HM, Li XJ (2005) Effect of chronic unpredictable mild stress on brain–pancreas relative protein in rat brain and pancreas. Behav Brain Res 165:63–71

    Article  PubMed  CAS  Google Scholar 

  3. Biessels GJ, Kapella AC, Bravenboer B, Erkelens DW, Gispen WH (1994) Cerebral function in diabetes mellitus. Diabetologia 37:643–650

    Article  PubMed  CAS  Google Scholar 

  4. Margolis RU, Altszuler N (1967) Insulin in the cerebrospinal fluid. Nature 215:1375–1376

    Article  PubMed  CAS  Google Scholar 

  5. Woods SC, Porte DJ (1977) Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am J Physiol 233:E331–E334

    PubMed  CAS  Google Scholar 

  6. Szabo O, Szabo AJ (1972) Evidence for an insulin sensitive receptor in the central nervous system. Am J Physiol 223:1349–1353

    PubMed  CAS  Google Scholar 

  7. Storlien L, Bellingham WP, Martin GM (1975) Localization of CNS glucoregulatory insulin receptors within the ventromedial hypothalamus. Brain Res 96:156–160

    Article  PubMed  CAS  Google Scholar 

  8. Dorn A, Bernstein HG, Hahn HJ, Ziegler M, Rummelfanger H (1981) Insulin immunohistochemistry of rodent CNS: apparent species differences but good correlation with radioimmunological data. Histochem 71:609–616

    Article  CAS  Google Scholar 

  9. Zhao WQ, Chen H, Quon MJ, Alkon DL (2004) Insulin and the insulin receptor in experimental models of learning and memory. Eur J Pharmacol 490:71–81

    Article  PubMed  CAS  Google Scholar 

  10. Singh P, Jain A, Kaur G (2004) Impact of hypoglycemia and diabetes on CNS: correlation of mitochondrial oxidative stress with DNA damage. Mol Cell Biochem 260:153–159

    Article  PubMed  CAS  Google Scholar 

  11. Auer RN (2004) Hypoglycemic brain damage. Metab Brain Dis 19:169–175

    Article  PubMed  Google Scholar 

  12. Auer RN, Kalimo H, Olsson Y, Wieloch T (1985) The dentate gyrus in hypoglycemia. Pathology implicating excitotoxin-mediated neuronal necrosis. Acta Neuropathol 67:279–288

    Article  PubMed  CAS  Google Scholar 

  13. Bestetti G, Rossi GL (1980) Hypothalamic lesions in rats with long-term streptozotocin-induced diabetes mellitus. A semiquantitative light-and electron -microscopic study. Acta Neuropathol 52:119–127

    Article  PubMed  CAS  Google Scholar 

  14. Bestetti G, Rossi GL (1982) Hypothalamic changes in diabetic Chinese hamsters. A semiquantitative, light and electron microscopic study. Lab Invest 47:516–522

    PubMed  CAS  Google Scholar 

  15. Garris DR, Diani AR, Smith C, Gerritsen GC (1982) Depopulation of the ventromedial hypothalamic nucleus in the diabetic Chinese hamster. Acta Neuropathol 56:63–66

    Article  PubMed  CAS  Google Scholar 

  16. Luse SA (1970) The ultrastructure of the brain in the diabetic Chinese hamster with special reference to synaptic abnormalities. Electroencephalogr Clin Neurophysiol 29:410

    PubMed  CAS  Google Scholar 

  17. Mukai N, Hori S, Pomeroy M (1980) Cerebral lesions in rats with streptozotoci- induced diabetes. Acta Neuropathol 51:79–84

    Article  PubMed  CAS  Google Scholar 

  18. Herbert V, Lau KS, Gottlieb CW, Bleicher SJ (1965) Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab 25:1375–1384

    Article  PubMed  CAS  Google Scholar 

  19. Gasparini L, Netzer WJ, Greengard P, Xu H (2002) Does insulin dysfunction play a role in Alzheimer’s disease? Trends Pharmacol Sci 23:288–293

    Article  PubMed  CAS  Google Scholar 

  20. Snyder EY, Kim SV (1980) Insulin: is it a nerve survival factor? Brain Res 196:565–574

    Article  PubMed  CAS  Google Scholar 

  21. Baskin DG, Porte D Jr, Guest K, Dorsa DM (1983) Regional concentrations of insulin in the rat brain. Endocrinology 112:898–903

    Article  PubMed  CAS  Google Scholar 

  22. Schulingkamp RJ, Pagano TC, Hung D, Raffa RB (2000) Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci Biobehav Rev 24:855–872

    Article  PubMed  CAS  Google Scholar 

  23. Unger JW, Livingston JN, Moss AM (1991) Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. Prog Neurobiol 36:343–362

    Article  PubMed  CAS  Google Scholar 

  24. Schechter R, Sadiq HF, Devaskar SU (1990) Insulin and insulin mRNA are detected in neuronal cell cultures maintained in an insulin-free/serum-free medium. J Histochem Cytochem 38:829–836

    PubMed  CAS  Google Scholar 

  25. Zhao WQ, Chen H, Xu H, Moore E, Meiri N, Quon MJ, Alkon DC (1999) Brain insulin receptors and spatial memory. J Biol Chem 274:34893–34902

    Article  PubMed  CAS  Google Scholar 

  26. Moxham CP, Duronio V, Jacobs S (1989) Insulin-like growth factor I receptor beta-subunit heterogeneity. Evidence for hybrid tetramers composed of insulin-like growth factor I and insulin receptor heterodimers. J Biol Chem 264:13238–13244

    PubMed  CAS  Google Scholar 

  27. Jonas E, Knox RJ, Smith TC, Wayne NL, Connor JA, Kaczmarek LK (1997) Regulation by insulin of a unique neuronal Ca2+ pool and of neuropeptide secretion. Nature 385:343–346

    Article  PubMed  CAS  Google Scholar 

  28. Recio-Pinto E, Lang FF, Ishii DN (1984) Insulin and insulin-like growth factor II permit nerve growth factor binding and the neurit formation response in cultured human neuroblastoma cells. Proc Natl Acad Sci USA 81:2562–2566

    Article  PubMed  CAS  Google Scholar 

  29. Wan Q, Xiong ZG, Man HY, Ackerley CA, Braunton J, Lu WY, Becker LE, MacDonald JF, Wang YT (1997) Recruitment of functional GABA(A) receptors to postsynaptic domains by insulin. Nature 388:686–690

    Article  PubMed  CAS  Google Scholar 

  30. Zheng WH, Kar S, Quirion R (2002) Insulin-like growth factor-1-induced phosphorylation of transcription factor FKHRL1 is mediated by phosphatidylinositol 3-kinase/Akt kinase and role of this pathway in insulin-like growth factor-1-induced survival of cultured hippocampal neurons. Mol Pharmacol 62:225–233

    Article  PubMed  CAS  Google Scholar 

  31. Hooghe-Peters EL, Meda P, Orci L (1981) Co-culture of nerve cells and pancreatic islets. Brain Res 227:287–292

    PubMed  CAS  Google Scholar 

  32. Magarinos AM, Jain K, Blount ED, Reagan L, Smith BH, McEwen BS (2001) Peritoneal implantation of macroencapsulated porcine pancreatic islets in diabetic rats ameliorates severe hyperglycemia and prevents retraction and simplification of hippocampal dendrites. Brain Res 902:282–287

    Article  PubMed  CAS  Google Scholar 

  33. McNay EC, Fries TM, Gold PE (2000) Decreases in rat extracellular hippocampal glucose concentration associated with cognitive demand during a spatial task. Proc Natl Acad Sci USA 97:2881–2885

    Article  PubMed  CAS  Google Scholar 

  34. McNay EC, McCarthy RC, Gold PE (2001) Fluctuations in brain glucose concentration during behavioral testing: dissociations between brain areas and between brain and blood. Neurobiol Learn Mem 75:325–337

    Article  PubMed  CAS  Google Scholar 

  35. Wozniak M, Rydzewski B, Baker SP, Raizada MK (1993) The cellular and physiological actions of insulin in the central nervous system. Neurochem Int 22:1–10

    Article  PubMed  CAS  Google Scholar 

  36. Henneberg N, Hoyer S (1995) Desensitization of the neuronal insulin receptor: a new approach in the etiopathogenesis of late-onset sporadic dementia of the Alzheimer type (SDAT)? Arch Gerontol Geriatr 21:63–74

    Article  PubMed  CAS  Google Scholar 

  37. Hoyer S, Prem L, Sorbi S, Amaducci L (1993) Stimulation of glycolytic key enzymes in cerebral cortex by insulin. Neuro Rep 4:991–993

    CAS  Google Scholar 

  38. Wree A (1991) Local cerebral glucose utilization in the brain of old learning impaired rats. Histochemistry 95:591–603

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the National Nature Science Foundation of China (No. 30270528), 973-Program of the Ministry of Science and Technology, and Research Funds from Ministry of Education of China, No. 20020001082 and 985 and 211 Projects.

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Authors and Affiliations

  1. Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University Health Science Center, Xueyuan Road no. 38, Beijing, 100083, China

    Yan-Hua Lin, Lu Tie & Xue-Jun Li

  2. Department of Psychiatry, Graduate School of Behavioral and Cognitive Neurosciences, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700, Groningen, RB, The Netherlands

    Yan-Hua Lin, Christel Westenbroek & Gert J. Ter Horst

  3. School of Pharmaceutical Science, Peking University, Beijing, 100083, China

    Ai-Hua Liu

  4. National Research Institute for Family Planning, Beijing, 100081, China

    He-Ming Yu

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  1. Yan-Hua Lin
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  2. Christel Westenbroek
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  3. Lu Tie
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  4. Ai-Hua Liu
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  7. Xue-Jun Li
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Correspondence to Xue-Jun Li.

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Lin, YH., Westenbroek, C., Tie, L. et al. Effects of Glucose, Insulin, and Supernatant from Pancreatic β-cells on Brain–Pancreas Relative Protein in Rat Hippocampus. Neurochem Res 31, 1417–1424 (2006). https://doi.org/10.1007/s11064-006-9193-9

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  • DOI: https://doi.org/10.1007/s11064-006-9193-9

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