Rat fibroblast cells overexpressing kinase-inactive human insulin receptors are insulin responsive: influence of growth conditions.

Abstract:

:The effects of insulin to stimulate metabolic and mitogenic responses were examined in Rat 1 fibroblast cells that overexpressed either normal (HIRc) or kinase-deficient human insulin receptors. When studied at the optimal growth stage for each cell line, insulin-stimulated responses measured in cells containing kinase-defective receptors with a Lys1018-Ala1018 substitution in the ATP-binding site of the kinase domain (A/K1018). Maximal insulin responsiveness for all these effects, measured as fold-increase over basal, was comparable in parental and HIRc cells (1.8- to 2.4-fold increases). Relative insulin responsiveness for all effects was greatest in A/K 1018 cells. One clone (AK-I) expressing a similar number of kinase-inactive receptors as in the HIRc cells displayed maximal responsiveness of 3.6- to 5.5-fold increases. A second A/K cell line containing 1/10 the number of kinase-inactive receptors displayed responsiveness intermediate between AK-I and parental or HIRc cells (1.5- to 4.8-fold increases). Both clones of kinase-deficient A/K1018 cells displayed impaired insulin sensitivity compared with HIRc cells. These findings suggest that expression of insulin receptor kinase activity is a determinant of insulin sensitivity but not necessarily of the final biological responsiveness of cells to insulin.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Wong EH,Tan CH,Khoo HE,Ng FH,Lim KL,Ciaraldi TP

doi

10.1210/endo.136.4.7534700

subject

Has Abstract

pub_date

1995-04-01 00:00:00

pages

1459-67

issue

4

eissn

0013-7227

issn

1945-7170

journal_volume

136

pub_type

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