Hepatic insulin sensitizing substance: A novel 'sensocrine' mechanism to increase insulin sensitivity in anaesthetized rats

Robert Porszasz, Gyorgyi Legvari, Tunde Pataki, Judith Szilvassy, Jozsef Nemeth, Peter Kovacs, Gyorgy Paragh, Janos Szolcsanyi, Zoltan Szilvassy

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

1. We recently described the sensory nitrergic nature of the hepatic insulin sensitizing substance (HISS) mechanism linked to postprandial activation of anterior hepatic plexus fibres in rabbits. This study is designed to assess the involvement of the sensory pathways in this mechanism. 2. Selective sensory denervation of the anterior hepatic plexus (AHP) was achieved by a 3-day perineurial treatment with 2% capsaicin solution in Wistar rats (230-250g). After 1 week, hyperinsulinaemic (100 μU kg -1) euglycaemic (5.5 mmol kg -1) glucose clamp studies were performed to estimate insulin sensitivity. 3. The rats with regional AHP sensory denervation exhibited a significantly decreased insulin sensitivity, that is, 9.1 ± 1.0 mg kg -1 min -1 glucose reinstalled euglycaemia vs 13.3 ± 1.9 mg kg -1 min -1 glucose (P<0.01) in control rats. 4. Acute partial hepatic denervation by AHP cut was without effect on insulin sensitivity, whereas chronic hepatic denervation induced insulin resistance was similar to that achieved by regional AHP capsaicin treatment. 5. Intraportal administration of L-NAME (10 mg kg -1) decreased, whereas capsaicin (0.3 mg kg -1 min -1) increased insulin sensitivity. Neither atropine (1 mg kg -1) nor acetylcholine (1-10 μg mg min -1) produced any significant effect. In animals with preceding regional capsaicin desensitization, none of the pharmacological manoeuvres modified the resulting insulin-resistant state. 6. Cysteamine (200 mg kg -1 s.c.) is known to cause functional somatostatin depletion-induced insulin resistance similar to that produced by either chronic partial hepatic denervation or perineurial AHP capsaicin desensitization. Intraportal capsaicin (0.3 mg kg -1 min -1) was unable to modify insulin resistance achieved by cysteamine. 7. We conclude that capsaicin-sensitive sensory fibres play a crucial role in neurogenic insulin sensitization known as the HISS mechanism without involvement of anatomical reflex-mediated circuits. The results also suggest that HISS is identical to somatostatin of AHP sensory neural origin.

Original languageEnglish
Pages (from-to)1171-1179
Number of pages9
JournalBritish journal of pharmacology
Volume139
Issue number6
DOIs
Publication statusPublished - Jul 2003

Keywords

  • Capsaicin
  • Denervation
  • Hepatic insulin sensitizing substance
  • Hyperinsulinaemic euglycaemic glucose clamp
  • Insulin resistance
  • Rat
  • Sensory nerves

ASJC Scopus subject areas

  • Pharmacology

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