Tyrosine Kinase Activity of Liver Insulin Receptor is Inhibited in Rats at Term Gestation

Overview

Journal Biochem J

Specialty Biochemistry

Date 1989 Oct 1

PMID 2690816

Citations 2

Authors

C Martinez

P Ruiz

A Andres

J Satrustegui

J M Carrascosa

Affiliations

Soon will be listed here.

Abstract

Late gestation is associated with insulin resistance in rats and humans. It has been reported that rats at term gestation show active hepatic gluconeogenesis and glycogenolysis, and diminished lipogenesis, despite normal or mildly elevated plasma insulin concentrations, indicating a state of resistance to the hormone action. Since autophosphorylation of the insulin receptor has been reported to play a key role in the hormone signal transduction, we have partially purified plasma-membrane liver insulin receptors from virgin and 22-day-pregnant rats and studied their binding and kinase activities. (1) Insulin binding to partially purified receptors does not appear to be influenced by gestation, as indicated by the observed KD and Bmax. values. (2) The rate of autophosphorylation and the maximal 32P incorporation into the receptor beta-subunit from pregnant rats at saturating concentrations of insulin are markedly decreased with respect to the corresponding values for virgin rats. (3) The diminished autophosphorylation rate was due to a decreased responsiveness of the kinase activity to the action of insulin. (4) Phosphorylation of the exogenous substrates casein and poly(Glu80Tyr20) by insulin-receptor kinase was also less when receptors from pregnant rats were used. These results show the existence of an impairment at the receptor kinase level of the insulin signalling mechanism that might be related to the insulin-resistant state characteristic of term gestation in rats.

Citing Articles

Impairment of the liver insulin receptor autoactivation cascade at full-term pregnancy in the rat.

Martinez C, Molero J, Ruiz P, Del Arco A, Andres A, Carrascosa J Biochem J. 1995; 311 ( Pt 2):523-9.

PMID: 7487890 PMC: 1136030. DOI: 10.1042/bj3110523.

Regulation of cyclic AMP synthesis and degradation is modified in rat liver at late gestation.

Martinez C, Ruiz P, Satrustegui J, Andres A, Carrascosa J Biochem J. 1992; 286 ( Pt 2):419-24.

PMID: 1326941 PMC: 1132915. DOI: 10.1042/bj2860419.

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