Skip to main content
Log in

Enhanced β-adrenergic receptors in the brain and pancreas during pancreatic regeneration in weanling rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Adrenergic stimulation has an important role in the pancreatic β-cell proliferation and insulin secretion. In the present study, we have investigated how sympathetic system regulates the pancreatic regeneration by analyzing Epinephrine (EPI), Norepinephrine (NE) and β-adrenergic receptor changes in the brain as well as in the pancreas. EPI and NE showed a significant decrease in the brain regions, pancreas and plasma at 72 hrs after partial pancreatectomy. We observed an increase in the circulating insulin levels at 72 hrs. Scatchard analysis using [3H] propranolol showed a significant increase in the number of both the low affinity and high affinity β-adrenergic receptors in cerebral cortex and hypothalamus of partially pancreatectomised rats during peak DNA synthesis. The affinity of the receptors decreased significantly in the low and high affinity receptors of cerebral cortex and the high affinity hypothalamic receptors. In the brain stem, low affinity receptors were increased significantly during regeneration whereas there was no change in the high affinity receptors. The pancreatic β-adrenergic receptors were also up regulated at 72 hrs after partial pancreatectomy. In vitro studies showed that β-adrenergic receptors are positive regulators of islet cell proliferation and insulin secretion. Thus our results suggest that the β-adrenergic receptors are functionally enhanced during pancreatic regeneration, which in turn increases pancreatic β-cell proliferation and insulin secretion in weanling rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ahren B: Autonomic regulation of islet hormone secretion-implications for health and disease. Diabetologia 43: 393–410, 2000

    Article  PubMed  CAS  Google Scholar 

  2. Burr IM, Slonim AE, Sharp R: Interactions of acetylcholine and epinephrine on the dynamics of insulin release in vitro. J. Clin. Invest 58: 230–239, 1976

    Article  CAS  Google Scholar 

  3. Campfield LA, Smith FJ: Modulation of insulin secretion by the autonomic nervous system. Brain Res. Bull 4: 103–107, 1980

    Article  Google Scholar 

  4. Bereiter DA, Rohner-Jeanrenaud F, Berthoud HR, Jeanrenaud B: CNS modulation of pancreatic endocrine funciton. Diabetologia 20: 417–425, 1981

    Article  PubMed  CAS  Google Scholar 

  5. Azmitia EC, Gannon P: Anatomy of serotonergic system in the primate and sub-primate brain. J Adv Neurol 43: 407–468, 1986

    CAS  Google Scholar 

  6. Ying Li, Xiaoyin Wu, Jinxia Zhu, Jin Yan, Chung Owyang: Hypothalamic regulation of pancreatic secretion is mediated by central cholinergic pathways in the rat. J Physiol 552: 571–587, 2003

    Article  PubMed  CAS  Google Scholar 

  7. Kiba T: Relationships between the autonomic nervous system and the pancreas including regulation of regeneration and apoptosis: recent developments. Pancreas 29 (2): e51–e58, 2004

    Google Scholar 

  8. Renuka TR, Ani V Das, Paulose CS: Alterations in the muscarinic M1 and M3 receptor gene expression in the brain stem during pancreatic regeneration and insulin secretion in weanling rats. Life Sci. 75: 2269–2280, 2004

    Article  PubMed  CAS  Google Scholar 

  9. Mohanan VV, Kaimal SB, Paulose CS: Decreased 5-HT1A receptor gene expression and 5-HT1A receptor protein in the cerebral cortex and brain stem during pancreatic regeneration in rats. Neurochem Res 30 (1): 25–32, 2005

    Article  PubMed  CAS  Google Scholar 

  10. Mohanan VV, Finla C, Paulose CS: Decreased 5-HT2c receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats. Mol Cell Biochem 272: 165–170, 2005

    Article  PubMed  CAS  Google Scholar 

  11. Renuka TR, Savitha B, Paulose CS: Muscarinic M1 and M3 receptor binding alterations in pancreas during pancreatic regeneration of young rats. Endocrine Res 31(4): 259–270, 2005

    Google Scholar 

  12. Porte, J: A receptor mechanism for the inhibition of insulin release by epinephrine in man. J.Clin Invest 46: 86–94, 1967(a)

    Google Scholar 

  13. McEvoy RC, Hegre OD: Syngeneic transplantation of fetal rat pancreas. II. Effects of insulin treatment on the growth and differentiation of pancreatic implants 15 days after transplantation. Diabetes. 27: 988–995, 1978

    CAS  Google Scholar 

  14. Porte DJ, Graber AL, Kuzuya T, Williams RH: The effect of Epinephrine on immunoreactive insulin levels in man. J. Clin Invest 45: 228–236, 1966(a)

    Google Scholar 

  15. Pearson KW, Scott D, Torrance B: Effects of partial surgical pancreatectomy in rats. Gastroenterol. 72: 469–473, 1977

    CAS  Google Scholar 

  16. Zangen DH, Bonner-Weir S, Lee CH, Latimer JB, Miller CP, Habener JF, Weir GC: Reduced insulin GLUT2 and IDX-1 in β-cells after partial pancreatectomy. Diabetes 46: 258–264, 1997

    Article  PubMed  CAS  Google Scholar 

  17. Glowinski J, Iversen LL: Regional studies of catecholamines in the rat brain: the disposition of [3H] Norepinephrine, [3H] DOPA in various regions of the brain. J. Neurochem 13: 655–669, 1966

    Article  PubMed  CAS  Google Scholar 

  18. Howell SL, Taylor KW: Potassium ions the secretion of insulin by islets of Langerhans incubated in vitro. Biochem J 108: 17–24, 1968

    Google Scholar 

  19. Jackson J, Pius SP, Thomas P, Paulose CS: Platelet monoamine changes in diabetic patients and streptozotocin induced diabetic rats. Current Science. 72: 137–139, 1997

    Google Scholar 

  20. Paulose CS, Dakshniamurti K, Packer S, Stephens LN: Sympathetic stimulation and hypertension in the pyridoxine-deficient adult rat. Hypertension 11: 387–391, 1988

    PubMed  CAS  Google Scholar 

  21. Lefkowtiz RJ, Williams LT: Catecholamine binding to the β-adrenergic receptor. Proc. Natl. Acad. Sci. USA. 74: 515–519, 1977

    Article  PubMed  ADS  Google Scholar 

  22. Lowry OH, Roserbrough NJ, Farr AL, Randall RJ: Protein measurement with Folin Phenol reagent. J Biol Chem 193: 265–275, 1951

    PubMed  CAS  Google Scholar 

  23. Scatchard G: The attraction of proteins for small molecules and ions. Ann. N. Y. Acad. Sci. 51: 660–672, 1949

    Article  CAS  ADS  Google Scholar 

  24. Sjoholm A: α-adrenergic inhibition of fetal rat pancreatic β-cell replication, and insulin secretion is mediated through a pertussis toxin-sensitive G-protein regulating islet cAMP content by interleukin-1β. Biophys Biochem Res Commun 180: 152–155, 1991

    Article  CAS  Google Scholar 

  25. Schneider WC: Determination of nucleic acids in tissues by pentos analysis. (Ed.) Colowick, Kalpan. NY: academic Press, Methods in Enzymology 680–684, 1957

  26. Burton K: A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation deoxy ribonucleic acids. Biochem J 62: 315–323, 1955

    Google Scholar 

  27. Holst JJ, Schwartz TW, Knuhtsen S, Jensen SL, Nielsen OV: Autonomic control of the endocrine secretion from isolated, perfused pig pancreas. J Auton Nerv Sys 17: 71–84, 1986

    Article  CAS  Google Scholar 

  28. Chick WL, Lauris V, Flewlling JH, Andrews KA, Woodruff JM: Pancreatic beta cell culture: preparation of purified monolayers. Endocrinol 92: 212, 1975

    Google Scholar 

  29. King DL, Chick WL: Pancreatic β-cell replication: effects of hexose sugars. Endocrinol. 99: 1003–1009, 1976

    CAS  Google Scholar 

  30. Leahy JL, Bonner-Weir S, Weir GC: Minimal chronic hyperglycemia is a critical determinant of impaired insulin secretion after an incomplete pancreatectomy. J Clin Invest 81: 1407–14, 1988

    Article  PubMed  CAS  Google Scholar 

  31. Lohr M, Lubbersmeyer J, Otremba B, Klapdor R, Grossner D, Kloppel G: Increase in B-cells in the pancreatic remnant after partial pancreatectomy in pigs. An immunocytochemical and functional study. Virchows Arch B Cell Pathol Incl Mol Pathol 56: 277–86. 1989

    Google Scholar 

  32. Porte D, Jr: Beta adrenergic stimulation of insulin release in man. Diabetes 16: 150, 1967(b)

  33. Ahren B: The effects of epinephrine on islet hormone secretion in dog. Int. J. Pancreatol 3: 375–388, 1988

    PubMed  CAS  Google Scholar 

  34. Efendic S, Luft R, Cerasi E: Quantitative determination of the interaction between epinephrine and various insulin releases in man. Diabetes 27: 319–326, 1978

    PubMed  CAS  Google Scholar 

  35. Renstrom E, Ding W, Bokvist, Rorsman P: Neurotransmitter-induced inhibition of exocytosis in insulin secretory β-cells by activation of calcineurin. Neurone 17: 513–522, 1996

    Article  CAS  Google Scholar 

  36. Porte D, Jr, Williams RH: Inhibition of insulin release by norepinephrine in man. Science 152: 228, 1966(b)

    Google Scholar 

  37. Coore HG, Randle PJ: Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro. Biochem J 93: 66, 1964

    Google Scholar 

  38. Lackovic Z, Salkovic M, Kuci Z, Relja M: Effect of long lasting diabetes mellitus on rat and human brain monoamines. J Neurochem 54: 143–47, 1990

    Article  PubMed  CAS  Google Scholar 

  39. Chen C, Yang J: Effects of short and long-lasting diabetes mellitus on mouse brain monoamines. Brain Res 552: 175–179, 1991

    Article  PubMed  CAS  Google Scholar 

  40. Tasaka Y, Matsumoto H, Inoue Y, Hirata Y: Brain catecholamine concentration in hyperosmolar diabetic rats. Diabetic Res 19: 1–7, 1992

    CAS  Google Scholar 

  41. Malaisse WF, Malaisse-Lagae PH, Wright, Ashmore J: Effects of adrenergic and cholinergic agents upon insulin secretion in vitro. Endocrinol 80: 975, 1967

  42. Loubatieres A, Mariani MM, Chapal J: Insulino-seeretion etudiee sur le pancre'as isole et per-fuse du rat. II. Action des cateeholamines et des sub-stances bloquant les reeepteurs adrenergique. Diabetologia 6: 533, 1970

    Google Scholar 

  43. Bornstein SR, Ehrhart-Bornstein M, Scherbaum WA, Pfeiffer EF, Holst JJ: Effects of splanchnic nerve stimulation on the adrenal cortex may be mediated by chromaffin cells in a paracrine manner. Endocrinol 127: 900–906, 1990

    Article  CAS  Google Scholar 

  44. Oda S, Hagino A, Ohneda A, Sasaki Y, Tsuda T: Adrenergic modulation of pancreatic glucagons and insulin secretion in sheep. American J Physiol 254: R518–R523 1988

    Google Scholar 

  45. Nonogaki K: New insights into sympathetic regulation of glucose and fat metabolism. Diabetologia 43 (5): 533–49, 2000

    Article  PubMed  CAS  Google Scholar 

  46. Abraham A, Paulose CS: Age-related alterations in noradrenergic function in the brain stem of streptozotocin-diabetic rats. J Biochem Mol Bio Biophys 3: 171–176, 1999

    CAS  Google Scholar 

  47. Paulose CS, Padayatti PS, Sudha B: Neurotransmitter- Hormonal regulation of diabetes and liver regeneration. Comparative Endocrinology and Reproduction. Joy, K.P., Krishna, C.A., Haldar (Eds). Narosa Publishing House, NewDelhi, India, pp 559–568, 1999

  48. Padayatti PS, Paulose CS: Alpha2 adrenergic and high affinity serotonergic receptor changes in the brain stem of streptozotocin-induced diabetic rats. Life Sci 65: 403–414, 1999

    Article  PubMed  CAS  Google Scholar 

  49. Garris DR: Age and diabetes associated alterations in regional brain norepinephrine concentrations and adrenergic receptor populations in C57BL/KsJ mice. Dev Brain Res 51: 161–166, 1990

    Article  CAS  Google Scholar 

  50. Swenne I: Effects of cyclic AMP on DNA replication and protein biosynthesis in fetal rat islet of Langerhans maintained in tissue culture. Bioscience Reports 2: 867–876, 1982

    Google Scholar 

  51. Hosoda K, Fitzgerald LR, Vaidya VA, Feussner GK, Fishman PH, Duman RS: Regulation of β2-adrenergic receptor mRNA and gene transcription in rat C6 glioma cells: effects of agonist, forskolin, and protein synthesis inhibition. Mol Pharmacol 48: 206–211, 1995

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. S. Paulose.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Das, V.A., Robinson, R. & Paulose, C.S. Enhanced β-adrenergic receptors in the brain and pancreas during pancreatic regeneration in weanling rats. Mol Cell Biochem 289, 11–19 (2006). https://doi.org/10.1007/s11010-006-9142-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-006-9142-6

Key words

Navigation