Proinsulin C peptide obviates sympathetically mediated suppression of splenic lymphocyte activity in rats

Diabetologia. 2000 Dec;43(12):1512-7. doi: 10.1007/s001250051562.

Abstract

Aims/hypothesis: To investigate whether proinsulin C peptide influences sympathetic nerve activity directly or indirectly through parasympathetic nerve activity.

Methods: The proliferative response of splenic lymphocytes to Concanavalin A (ConA response) which is known to be suppressed by subjection of rats to footshock or intracerebroventricular injection of corticotropin-releasing factor through sympathetic nerve activation was measured. Effect of C peptide alone or before subjection to footshock or injection of corticotropin-releasing factor was examined.

Results: Intraperitoneal injection of C peptide was without effect on the basal ConA response, while subjection to footshock or injection of corticotropin-releasing factor lowered it. In contrast, prior injection of C peptide obviated the footshock and corticotropin-releasing factor-induced suppression of the response. When given intracerebroventricularly, C peptide was also effective at much smaller doses. Prior injection of atropine cancelled the C-peptide effects.

Conclusion/interpretation: Our results indicate that C peptide counteracts the sympathetic nerve-mediated suppression of splenic lymphocyte proliferation in an atropine-sensitive manner. Thus, C peptide probably activates the parasympathetic nervous system through the afferent mechanism, that in turn antagonizes the sympathetic nerve-mediated suppression of splenic lymphocyte functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atropine / pharmacology
  • C-Peptide / administration & dosage
  • C-Peptide / pharmacology*
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology*
  • Corticotropin-Releasing Hormone / administration & dosage
  • Corticotropin-Releasing Hormone / pharmacology
  • Electroshock
  • Female
  • Humans
  • Immunosuppression Therapy
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Lymphocyte Activation / drug effects*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*
  • Rats
  • Rats, Wistar
  • Spleen / immunology
  • Spleen / innervation*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology*

Substances

  • C-Peptide
  • Atropine
  • Corticotropin-Releasing Hormone