Insulin sensitization induced by oral cicletanine in conscious rabbits

Barna Peitl, J. Németh, Csaba Pankucsi, Z. Szilvássy

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The endogenous insulin sensitizing machinery termed the hepatic insulin sensitizing substance (HISS) mechanism has been shown to be nitrergic and linked to sensory fibers in the anterior hepatic plexus. We studied whether this mechanism could pharmacologically be exploited by cicletanine, a cGMP-PDE inhibitor antihypertensive drug, in conscious rabbits. Whole body insulin sensitivity and peripheral glucose uptake were determined by hyperinsulinaemic euglycaemic glucose clamping, and cardiac radiolabelled deoxyglucose (DOG) uptake in neurogenic, achieved by perineurial capsaicin treatment of the anterior hepatic plexus through defunctionalization of hepatic sensory fibers, and metabolic, induced by dietary hypercholesterolemia, insulin resistance models after single oral doses of cicletanine (3, 10 and 30 mg kg-1) or rosiglitazone (3 mg kg-1). The effect of cicletanine on cardiac and vascular tissue NO, cGMP, cAMP was measured by means of spin trapping technique and radioimmunoassay, respectively. Insulin sensitivity and peripheral DOG uptake were significantly increased by 10 and 30 mg kg-1 cicletanine in both healthy and hypercholesterolaemic rabbits, but not in those with neurogenic insulin resistance. Rosiglitazone had no effect in healthy and neurogenic insulin resistant rabbits although it improved insulin sensitivity in hypercholesterolemic animals. The 10 mg kg-1 cicletanine dose induced no change in either cardiac or vascular tissue NO, cGMP or cAMP concentrations. Nevertheless, at a dose of 30 mg kg-1 producing an insulin sensitizing effect of approximately the same amplitude as seen with 10 mg kg-1, the drug significantly increased tissue NO and cGMP concentrations. Oral cicletanine attains its insulin sensitizing effect at doses lower than those necessary to activate the NO-cGMP pathway in the cardiovascular system. This metabolic effect requires functional integrity of hepatic sensory nerves.

Original languageEnglish
Pages (from-to)429-439
Number of pages11
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume373
Issue number6
DOIs
Publication statusPublished - Sep 2006

Fingerprint

rosiglitazone
Insulin Resistance
Insulin
Rabbits
Liver
Glucose Clamp Technique
Deoxyglucose
Blood Vessels
Spin Trapping
Capsaicin
Cardiovascular System
Hypercholesterolemia
Antihypertensive Agents
Radioimmunoassay
cicletanine
Glucose
Pharmaceutical Preparations

Keywords

  • Antihypertensive drug
  • Capsaicin
  • Cicletanine
  • Cyclic nucleotide
  • Hyperinsulinaemic euglycaemic glucose clamp
  • Neurogenic insulin resistance
  • Nitric oxide
  • Rosiglitazone

ASJC Scopus subject areas

  • Pharmacology

Cite this

Insulin sensitization induced by oral cicletanine in conscious rabbits. / Peitl, Barna; Németh, J.; Pankucsi, Csaba; Szilvássy, Z.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 373, No. 6, 09.2006, p. 429-439.

Research output: Contribution to journalArticle

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