Glucose-dependent insulinotropic peptide: Differential effects on hepatic artery vs. portal vein endothelial cells

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Glucose-dependent insulinotropic peptide (GIP) has been reported to have opposing effects on splanchnic blood flow. GIP infusion in dogs results in an increase in portal vein circulation but a drop in hepatic artery blood flow. In an effort to evaluate whether these different responses were related to intrinsic differences in GIP effects, we isolated canine hepatic artery (HAEC) and portal vein endothelial cells (PVEC). We report that there are differences in GIP activation of the signal transduction pathways in these two cell types. GIP stimulates secretion of endothelin-1 (ET-1), a potent vasoconstrictor, from HAEC (EC50 0.28 nM) but not from PVEC. This effect could be abolished by preventing a rise in intracellular calcium, demonstrating the calcium dependence of GIP-induced ET-1 secretion from HAEC. The GIP effect was specific, as a GIP receptor antagonist blocked it. In contrast, GIP stimulated nitric oxide production from PVEC (EC50 0.09 nM) but not from HAEC. Taken together, our data demonstrate distinct differences in GIP effects on HAEC from those on PVEC. We conclude that differences in GIP stimulation of ET-1 vs. nitric oxide production in different vascular beds may account for some of the observed differences in its physiological effects.

Original languageEnglish (US)
Pages (from-to)E773-E779
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume286
Issue number5 49-5
DOIs
StatePublished - May 1 2004

Fingerprint

Gastric Inhibitory Polypeptide
Hepatic Artery
Endothelial cells
Portal Vein
Endothelial Cells
Endothelin-1
Nitric Oxide
Blood
Calcium
Signal transduction
Peptide Receptors
Viscera
Vasoconstrictor Agents
Blood Vessels
Canidae
Signal Transduction

Keywords

  • Canine
  • Endothelin
  • Nitric oxide
  • Receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

@article{9aadd0da60104d56b24fac126afb5a5d,
title = "Glucose-dependent insulinotropic peptide: Differential effects on hepatic artery vs. portal vein endothelial cells",
abstract = "Glucose-dependent insulinotropic peptide (GIP) has been reported to have opposing effects on splanchnic blood flow. GIP infusion in dogs results in an increase in portal vein circulation but a drop in hepatic artery blood flow. In an effort to evaluate whether these different responses were related to intrinsic differences in GIP effects, we isolated canine hepatic artery (HAEC) and portal vein endothelial cells (PVEC). We report that there are differences in GIP activation of the signal transduction pathways in these two cell types. GIP stimulates secretion of endothelin-1 (ET-1), a potent vasoconstrictor, from HAEC (EC50 0.28 nM) but not from PVEC. This effect could be abolished by preventing a rise in intracellular calcium, demonstrating the calcium dependence of GIP-induced ET-1 secretion from HAEC. The GIP effect was specific, as a GIP receptor antagonist blocked it. In contrast, GIP stimulated nitric oxide production from PVEC (EC50 0.09 nM) but not from HAEC. Taken together, our data demonstrate distinct differences in GIP effects on HAEC from those on PVEC. We conclude that differences in GIP stimulation of ET-1 vs. nitric oxide production in different vascular beds may account for some of the observed differences in its physiological effects.",
keywords = "Canine, Endothelin, Nitric oxide, Receptor",
author = "Ding, {Ke Hong} and Qing Zhong and Jianrui Xu and Isales, {Carlos M.}",
year = "2004",
month = "5",
day = "1",
doi = "10.1152/ajpendo.00507.2003",
language = "English (US)",
volume = "286",
pages = "E773--E779",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5 49-5",

}

TY - JOUR

T1 - Glucose-dependent insulinotropic peptide

T2 - Differential effects on hepatic artery vs. portal vein endothelial cells

AU - Ding, Ke Hong

AU - Zhong, Qing

AU - Xu, Jianrui

AU - Isales, Carlos M.

PY - 2004/5/1

Y1 - 2004/5/1

N2 - Glucose-dependent insulinotropic peptide (GIP) has been reported to have opposing effects on splanchnic blood flow. GIP infusion in dogs results in an increase in portal vein circulation but a drop in hepatic artery blood flow. In an effort to evaluate whether these different responses were related to intrinsic differences in GIP effects, we isolated canine hepatic artery (HAEC) and portal vein endothelial cells (PVEC). We report that there are differences in GIP activation of the signal transduction pathways in these two cell types. GIP stimulates secretion of endothelin-1 (ET-1), a potent vasoconstrictor, from HAEC (EC50 0.28 nM) but not from PVEC. This effect could be abolished by preventing a rise in intracellular calcium, demonstrating the calcium dependence of GIP-induced ET-1 secretion from HAEC. The GIP effect was specific, as a GIP receptor antagonist blocked it. In contrast, GIP stimulated nitric oxide production from PVEC (EC50 0.09 nM) but not from HAEC. Taken together, our data demonstrate distinct differences in GIP effects on HAEC from those on PVEC. We conclude that differences in GIP stimulation of ET-1 vs. nitric oxide production in different vascular beds may account for some of the observed differences in its physiological effects.

AB - Glucose-dependent insulinotropic peptide (GIP) has been reported to have opposing effects on splanchnic blood flow. GIP infusion in dogs results in an increase in portal vein circulation but a drop in hepatic artery blood flow. In an effort to evaluate whether these different responses were related to intrinsic differences in GIP effects, we isolated canine hepatic artery (HAEC) and portal vein endothelial cells (PVEC). We report that there are differences in GIP activation of the signal transduction pathways in these two cell types. GIP stimulates secretion of endothelin-1 (ET-1), a potent vasoconstrictor, from HAEC (EC50 0.28 nM) but not from PVEC. This effect could be abolished by preventing a rise in intracellular calcium, demonstrating the calcium dependence of GIP-induced ET-1 secretion from HAEC. The GIP effect was specific, as a GIP receptor antagonist blocked it. In contrast, GIP stimulated nitric oxide production from PVEC (EC50 0.09 nM) but not from HAEC. Taken together, our data demonstrate distinct differences in GIP effects on HAEC from those on PVEC. We conclude that differences in GIP stimulation of ET-1 vs. nitric oxide production in different vascular beds may account for some of the observed differences in its physiological effects.

KW - Canine

KW - Endothelin

KW - Nitric oxide

KW - Receptor

UR - http://www.scopus.com/inward/record.url?scp=1942454241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1942454241&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00507.2003

DO - 10.1152/ajpendo.00507.2003

M3 - Article

C2 - 14709420

AN - SCOPUS:1942454241

VL - 286

SP - E773-E779

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5 49-5

ER -