Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Putrescine and Cadaverine Enhance Insulin Secretion of Mouse Pancreatic ${\beta}$-cell Line

  • Park, Hyo-Eun (Department of Biological Science, Gachon University) ;
  • Kim, Jae-Young (Department of Biological Science, Gachon University)
  • Received : 2012.06.04
  • Accepted : 2012.07.16
  • Published : 2012.09.30
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Abstract

We examined the effects of polyamines such as putrescine and cadaverine on the biosynthesis and secretion of insulin in the mouse pancreatic ${\beta}$-cell line, MIN-6. Basal insulin secretion (BIS) and glucose-stimulated insulin secretion (GSIS) from the MIN-6 cells were significantly increased by 20 min- or 24 h-treatment with micromolar concentrations of polyamines. To determine whether the enhancement was due to increase of insulin production by polyamines, we investigated the insulin mRNA and protein production. Both insulin mRNA and protein production were found to be not significantly affected by the polyamine treatment. Next, we examined the expression of several transcription factors (TFs) related to insulin synthesis and secretion in order to identify upstream events responsible for the promotion of insulin secretion of MIN6 cells by polyamines. Of the 6 TFs tested, MafA was induced by treatment of polyamines. MafA mRNA and protein expressions increased with treatment of polyamines. Overall results suggest that cadaverine and putrescine promote the insulin secretion process rather than the insulin biosynthesis from MIN6 cells. Also MafA may be involved in the enhanced insulin secretion process. Further studies are needed to elucidate the underlying mechanisms for promotion of insulin secretion by polyamines.

Keywords

References

  1. Aguayo-Mazzucato C, Koh A, El Khattabi I, Li WC, Toschi E, Jermendy A, Juhl K, Mao K, Weir GC, Sharma A, Bonner-Weir S. Mafa expression enhances glucose-responsive insulin secretion in neonatal rat beta cells. Diabetologia. 2011. 54: 583-593. https://doi.org/10.1007/s00125-010-2026-z
  2. Bliss CR, Sharp GW. Glucose-induced insulin release in islets of young rats: time-dependent potentiation and effects of 2-bromostearate. Am J Physiol. 1992. 263: E890-E896.
  3. Brixel LR, Monteilh-Zoller MK, Ingenbrandt CS, Fleig A, Penner R, Enklaar T, Zabel BU, Prawitt D. TRPM5 regulates glucose-stimulated insulin secretion. Pflugers Arch Eur J Physiol. 2010. 460: 69-76. https://doi.org/10.1007/s00424-010-0835-z
  4. D'Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE. Production of pancreatic hormone endocrine cells from human embryonic stem cells. Nat Biotechnol. 2006. 24: 1392-1401. https://doi.org/10.1038/nbt1259
  5. Dela Vega AL, Delcour AH. Cadaverine induces closing of E. coli porins. EMBO J. 1995. 14: 6058-6065.
  6. Hellerstrom C, Swenne I. Functional maturation and proliferation of fetal pancreatic beta-cells. Diabetes. 1991. 40: 89-93.
  7. Hougaard DM, Nielsen JH, Larsson L-I. Localization and bio-synthesis of polyamines in insulin-producing cells. Biochem J. 1986. 238: 43-47.
  8. Janne J, Alhonen L, Keinanen TA, pietila M, Uimari A, Pirinen E, Hyvonen MT, Jarvinen A. Animal disease models generated by genetic engineering of polyamine metabolism. J Cell Mol Med. 2005. 9: 865-882. https://doi.org/10.1111/j.1582-4934.2005.tb00385.x
  9. Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart NG, Cunningham J, Agulnick AD, D'Amour KA, Carpenter MK, Baetge EE. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol. 2008. 26: 443-452. https://doi.org/10.1038/nbt1393
  10. Miyazaki J, Araki K, Yamato E. Establishment of a pancreatic beta cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms. Endocrinology. 1990. 127: 126-132. https://doi.org/10.1210/endo-127-1-126
  11. Nishimura W, Kondo T, Salameh T, El Khattabi I, Dodge R, Bonner-Weir S, Sharma A. A switch from MafB to MafA expression accompanies differentiation to pancreatic betacells. Dev Biol. 2006. 293: 526-539. https://doi.org/10.1016/j.ydbio.2006.02.028
  12. Ohtani M, Mizuno I, Kojima Y, Ishikawa Y, Sodeno M, Asakura Y, Samejima K, Oka T. Spermidine regulates insulin synthesis and cytoplasmic $Ca^{2+}$ in mouse beta-TC6 insulinoma cells. Cell Structure Function. 2009. 34: 105-113. https://doi.org/10.1247/csf.09008
  13. Pegg AE. Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy. Cancer Therapy. 1988. 48: 759-774.
  14. Sjoholm A, Welsh N, Sandler S, Hellerstrom C. Role of polyamines in mitogenic and secretory responses of pancreatic ${\beta}$-cells to growth factors. Am J Physiol. 1990. 259: C828-C833.
  15. Thams P, Capito K, Hedeskov CJ. An inhibitory role for poly-amines in protein kinase C activation and insulin secretion in mouse pancreatic islets. Biochem J. 1986. 237: 131-138.
  16. Thomas T, Thomas TJ. Polyamine metabolism and cancer. J Cell Mol Med. 2003. 7: 113-126. https://doi.org/10.1111/j.1582-4934.2003.tb00210.x
  17. Wang H, Brun T, Kataoka K, Sharma AJ, Wollheim CB. MAFA controls genes implicated in insulin biosynthesis and secretion. Diabetologia. 2007. 50: 348-358. https://doi.org/10.1007/s00125-006-0490-2
  18. Welsh N. A role for polyamines in glucose-stimulated insulin-gene expression. Biochem J. 1990. 271: 393-397.
  19. Welsh N, Sjoholm A. Polyamines and insulin production in isolated mouse pancreatic islets. Biochem J. 1988. 252: 701-707.
  20. Williams K. Interactions of polyamines with ion channels. Biochem J. 1997. 325: 289-297.
  21. Zhang C, Moriguchi T, Kajihara M, Esaki R, Harada A, Shimohata H, Oishi H, Hamada M, Morito N, Hasegawa K, Kudo T, Engel JD, Yamamoto M, Takahashi S. MafA is a key regulator of glucose-stimulated insulin secretion. Mol Cell Biol. 2005. 25: 4969-4976. https://doi.org/10.1128/MCB.25.12.4969-4976.2005