Korean J Physiol Pharmacol.  1999 Dec;3(6):571-578.

Effects of protein kinase C modulation on hepatic hemodynamics and glucoregulation

Affiliations
  • 1Department of Physiology, Yonsei University, Wonju College of Medicine, Wonju, Korea.
  • 2Department of Institute of Medical Engineering, Yonsei University, Wonju College of Medicine, Wonju 220-701, Korea.
  • 3Department of Physiology, Stritch School of Medicine, Loyola university of Chicago 2160 South First Avenue Maywood, IL 60153, USA.

Abstract

This study evaluated the effects of PKC activation using phorbol 12-myristate 13-acetate (PMA) and PKC inhibition using the isoquinoline sulfomide derivative H-7 on hemodynamics and glucoregulation in the isolated perfused rat liver. Livers were isolated from fed male Holtzman rats and perfused with Krebs Ringer bicarbonate solution under a constant flow of 50 ml/min at 35degreeC. Portal vein pressure, glucose and lactate concentrations in the medium and oxygen consumption rates were continuously monitored by a Grass polygraph, YSI glucose and lactate monitors, and a YSI oxygen monitor, respectively. PMA at concentration of 2 to 200 nM increased the portal vein pressure, glucose and lactate production, but decreased oxygen consumption rate in a dose-dependent fashion. H-7 (200 micrometer) attenuated PMA (50 nM)-induced vasoconstriction (15.1+/-1.36 vs 10.56+/-1.17 mmHg), glucose production rate (91.3+/-6.15 vs 71.8+/-2.50 micromoles/g/hr), lactate production rate (72.4+/-6.82 vs 53.6+/-4.82 micromoles/g/hr) and oxygen consumption rate (33.7+/-1.41 vs 27.9+/-1.75 microliter/g/min). The effects of PMA were blocked either by addition of verapamil (9 micrometer) or perfusion with Ca2+-free KRB. These results suggest that the hemodynamic and glucoregulatory changes in the perfused rat liver are mediated by protein kinase C activation and require Ca2+ influx from the extracellular fluid.

Keyword

Protein kinase C; PMA; Perfused liver; Glucose output; Protal vein; Hepatocyte

MeSH Terms

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Animals
Extracellular Fluid
Glucose
Hemodynamics*
Hepatocytes
Humans
Lactic Acid
Liver
Male
Oxygen
Oxygen Consumption
Perfusion
Poaceae
Portal Vein
Protein Kinase C*
Protein Kinases*
Rats
Rats, Sprague-Dawley
Vasoconstriction
Verapamil
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Glucose
Lactic Acid
Oxygen
Protein Kinase C
Protein Kinases
Verapamil
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