HYPERINSULINEMIA CAUSES A PREFERENTIAL INCREASE IN HEPATIC P4501A2 ACTIVITY

CR Barnett, J Wilson, CR Wolf, Peter Flatt, C Ioannides

Research output: Contribution to journalArticle

Abstract

Male NEDH (New England Deaconess Hospital) rats were transplanted with a radiation-induced tumour from a donor male rat and were killed 18 days following transplantation. At the time of killing the insulinoma-bearing animals were severely hypoglycaemic but plasma ketone levels were normal. Insulinoma-bearing animals exhibited higher hepatic O-deethylation of ethoxyresorufin and N-demethylation of ethylmorphine activities when compared to control animals. Similarly, hepatic microsomal preparations from insulinoma-bearing rats were more efficient than control animals in converting the promutagen 2-amino-6-methyldipyrido[1,2-alpha:3',2']imidazole (Glu-P-1) to mutagenic intermediates in the Ames test. Immunoblot analysis employing polyclonal antibodies against the P4501A and P453A families revealed that insulinoma-bearing rats had higher hepatic P4501A2 apoprotein levels. No major differences in P4503A1 apoprotein levels between insulinoma-bearing and control rats were noted. Subcutaneous administration of insulin to male Wistar rats gave rise to a modest increase in ethoxyresorufin O-deethylase activity and in the ability to activate Glu-P-1 to mutagens in the Ames test. Immunoblot analysis revealed an increase in hepatic P4501A2 apoprotein levels following the treatment with insulin. It is concluded that insulinoma-bearing rats display high P4501A2 activity and the hyperinsulinaemia that characterize this condition is responsible for the effect. Moreover, administration of insulin to other strains of rat, such as Wistar, also enhances P4501A2 activity, presumably as a result of hyperinsulinaemia.
LanguageEnglish
Pages1255-1261
JournalBIiochemical Pharmacology
Volume43
Issue number6
Publication statusPublished - Mar 1992

Fingerprint

Hyperinsulinism
Insulinoma
2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole
Liver
Apoproteins
Insulin
Ethylmorphine
New England
Cytochrome P-450 CYP1A1
Mutagens
Ketones
Hypoglycemic Agents
Wistar Rats
Transplantation
Radiation
Antibodies
Neoplasms

Cite this

Barnett, CR., Wilson, J., Wolf, CR., Flatt, P., & Ioannides, C. (1992). HYPERINSULINEMIA CAUSES A PREFERENTIAL INCREASE IN HEPATIC P4501A2 ACTIVITY. BIiochemical Pharmacology, 43(6), 1255-1261.
Barnett, CR ; Wilson, J ; Wolf, CR ; Flatt, Peter ; Ioannides, C. / HYPERINSULINEMIA CAUSES A PREFERENTIAL INCREASE IN HEPATIC P4501A2 ACTIVITY. In: BIiochemical Pharmacology. 1992 ; Vol. 43, No. 6. pp. 1255-1261.
@article{37e853998e87414b8c98d537d7937eb4,
title = "HYPERINSULINEMIA CAUSES A PREFERENTIAL INCREASE IN HEPATIC P4501A2 ACTIVITY",
abstract = "Male NEDH (New England Deaconess Hospital) rats were transplanted with a radiation-induced tumour from a donor male rat and were killed 18 days following transplantation. At the time of killing the insulinoma-bearing animals were severely hypoglycaemic but plasma ketone levels were normal. Insulinoma-bearing animals exhibited higher hepatic O-deethylation of ethoxyresorufin and N-demethylation of ethylmorphine activities when compared to control animals. Similarly, hepatic microsomal preparations from insulinoma-bearing rats were more efficient than control animals in converting the promutagen 2-amino-6-methyldipyrido[1,2-alpha:3',2']imidazole (Glu-P-1) to mutagenic intermediates in the Ames test. Immunoblot analysis employing polyclonal antibodies against the P4501A and P453A families revealed that insulinoma-bearing rats had higher hepatic P4501A2 apoprotein levels. No major differences in P4503A1 apoprotein levels between insulinoma-bearing and control rats were noted. Subcutaneous administration of insulin to male Wistar rats gave rise to a modest increase in ethoxyresorufin O-deethylase activity and in the ability to activate Glu-P-1 to mutagens in the Ames test. Immunoblot analysis revealed an increase in hepatic P4501A2 apoprotein levels following the treatment with insulin. It is concluded that insulinoma-bearing rats display high P4501A2 activity and the hyperinsulinaemia that characterize this condition is responsible for the effect. Moreover, administration of insulin to other strains of rat, such as Wistar, also enhances P4501A2 activity, presumably as a result of hyperinsulinaemia.",
author = "CR Barnett and J Wilson and CR Wolf and Peter Flatt and C Ioannides",
year = "1992",
month = "3",
language = "English",
volume = "43",
pages = "1255--1261",
journal = "BIiochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier",
number = "6",

}

Barnett, CR, Wilson, J, Wolf, CR, Flatt, P & Ioannides, C 1992, 'HYPERINSULINEMIA CAUSES A PREFERENTIAL INCREASE IN HEPATIC P4501A2 ACTIVITY', BIiochemical Pharmacology, vol. 43, no. 6, pp. 1255-1261.

HYPERINSULINEMIA CAUSES A PREFERENTIAL INCREASE IN HEPATIC P4501A2 ACTIVITY. / Barnett, CR; Wilson, J; Wolf, CR; Flatt, Peter; Ioannides, C.

In: BIiochemical Pharmacology, Vol. 43, No. 6, 03.1992, p. 1255-1261.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HYPERINSULINEMIA CAUSES A PREFERENTIAL INCREASE IN HEPATIC P4501A2 ACTIVITY

AU - Barnett, CR

AU - Wilson, J

AU - Wolf, CR

AU - Flatt, Peter

AU - Ioannides, C

PY - 1992/3

Y1 - 1992/3

N2 - Male NEDH (New England Deaconess Hospital) rats were transplanted with a radiation-induced tumour from a donor male rat and were killed 18 days following transplantation. At the time of killing the insulinoma-bearing animals were severely hypoglycaemic but plasma ketone levels were normal. Insulinoma-bearing animals exhibited higher hepatic O-deethylation of ethoxyresorufin and N-demethylation of ethylmorphine activities when compared to control animals. Similarly, hepatic microsomal preparations from insulinoma-bearing rats were more efficient than control animals in converting the promutagen 2-amino-6-methyldipyrido[1,2-alpha:3',2']imidazole (Glu-P-1) to mutagenic intermediates in the Ames test. Immunoblot analysis employing polyclonal antibodies against the P4501A and P453A families revealed that insulinoma-bearing rats had higher hepatic P4501A2 apoprotein levels. No major differences in P4503A1 apoprotein levels between insulinoma-bearing and control rats were noted. Subcutaneous administration of insulin to male Wistar rats gave rise to a modest increase in ethoxyresorufin O-deethylase activity and in the ability to activate Glu-P-1 to mutagens in the Ames test. Immunoblot analysis revealed an increase in hepatic P4501A2 apoprotein levels following the treatment with insulin. It is concluded that insulinoma-bearing rats display high P4501A2 activity and the hyperinsulinaemia that characterize this condition is responsible for the effect. Moreover, administration of insulin to other strains of rat, such as Wistar, also enhances P4501A2 activity, presumably as a result of hyperinsulinaemia.

AB - Male NEDH (New England Deaconess Hospital) rats were transplanted with a radiation-induced tumour from a donor male rat and were killed 18 days following transplantation. At the time of killing the insulinoma-bearing animals were severely hypoglycaemic but plasma ketone levels were normal. Insulinoma-bearing animals exhibited higher hepatic O-deethylation of ethoxyresorufin and N-demethylation of ethylmorphine activities when compared to control animals. Similarly, hepatic microsomal preparations from insulinoma-bearing rats were more efficient than control animals in converting the promutagen 2-amino-6-methyldipyrido[1,2-alpha:3',2']imidazole (Glu-P-1) to mutagenic intermediates in the Ames test. Immunoblot analysis employing polyclonal antibodies against the P4501A and P453A families revealed that insulinoma-bearing rats had higher hepatic P4501A2 apoprotein levels. No major differences in P4503A1 apoprotein levels between insulinoma-bearing and control rats were noted. Subcutaneous administration of insulin to male Wistar rats gave rise to a modest increase in ethoxyresorufin O-deethylase activity and in the ability to activate Glu-P-1 to mutagens in the Ames test. Immunoblot analysis revealed an increase in hepatic P4501A2 apoprotein levels following the treatment with insulin. It is concluded that insulinoma-bearing rats display high P4501A2 activity and the hyperinsulinaemia that characterize this condition is responsible for the effect. Moreover, administration of insulin to other strains of rat, such as Wistar, also enhances P4501A2 activity, presumably as a result of hyperinsulinaemia.

M3 - Article

VL - 43

SP - 1255

EP - 1261

JO - BIiochemical Pharmacology

T2 - BIiochemical Pharmacology

JF - BIiochemical Pharmacology

SN - 0006-2952

IS - 6

ER -

Barnett CR, Wilson J, Wolf CR, Flatt P, Ioannides C. HYPERINSULINEMIA CAUSES A PREFERENTIAL INCREASE IN HEPATIC P4501A2 ACTIVITY. BIiochemical Pharmacology. 1992 Mar;43(6):1255-1261.