Direct evidence that the insulin receptor mediates a mitogenic response in cultured human fibroblasts

A. Conover, R. L. Hintz, Ronald (Ron) Rosenfeld

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

To define the role of the insulin receptor in mediating a mitogenic response in cultured human fibroblasts, the effects of specific monoclonal antibodies against the insulin and the type I IGF receptor on insulin-stimulated [3H]thymidine incorporation were investigated. Insulin stimulated [3H]thymidine incorporation in a biphasic fashion. In the first phase, a half-maximal effect was observed at 20 ng/ml, and a seemingly maximal effect was obtained at 100-1000 ng/ml. With 10 μg/ml insulin, a secondary increase in [3H]thymidine incorporation was seen which was similar to the maximal effect of IGF-I. These [3H]thymidine incorporation results were corroborated with cell replication studies. MC-51, a highly specific monoclonal antibody for the insulin receptor, inhibited the stimulation of [3H]thymidine incorporation by 25 ng/ml of insulin. AlphaIR-3, a monoclonal antibody specifically directed against the type I IGF receptor, had no significant effect on insulin-stimulated [3H]thymidine incorporation at low (10-1000 ng/ml) concentrations of insulin. However, alphaIR-3 interfered with the incremental increase in [3H]thymidine incorporation observed at 10-100 μg/ml insulin. These data demonstrate that insulin, at low concentrations, is capable of stimulating DNA synthesis and replication of human fibroblasts through interaction with its own receptor, while at supraphysiological concentrations, much of insulin's mitogenic effect is mediated through the type I IGF receptor.

Original languageEnglish (US)
Pages (from-to)59-63
Number of pages5
JournalHormone and Metabolic Research
Volume21
Issue number2
StatePublished - 1989
Externally publishedYes

Fingerprint

Insulin Receptor
Fibroblasts
Thymidine
Insulin
IGF Type 1 Receptor
Monoclonal Antibodies
DNA Replication
Insulin-Like Growth Factor I
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Direct evidence that the insulin receptor mediates a mitogenic response in cultured human fibroblasts. / Conover, A.; Hintz, R. L.; Rosenfeld, Ronald (Ron).

In: Hormone and Metabolic Research, Vol. 21, No. 2, 1989, p. 59-63.

Research output: Contribution to journalArticle

Conover, A. ; Hintz, R. L. ; Rosenfeld, Ronald (Ron). / Direct evidence that the insulin receptor mediates a mitogenic response in cultured human fibroblasts. In: Hormone and Metabolic Research. 1989 ; Vol. 21, No. 2. pp. 59-63.
@article{f6c79636e1b3423dbb7700c7336b334a,
title = "Direct evidence that the insulin receptor mediates a mitogenic response in cultured human fibroblasts",
abstract = "To define the role of the insulin receptor in mediating a mitogenic response in cultured human fibroblasts, the effects of specific monoclonal antibodies against the insulin and the type I IGF receptor on insulin-stimulated [3H]thymidine incorporation were investigated. Insulin stimulated [3H]thymidine incorporation in a biphasic fashion. In the first phase, a half-maximal effect was observed at 20 ng/ml, and a seemingly maximal effect was obtained at 100-1000 ng/ml. With 10 μg/ml insulin, a secondary increase in [3H]thymidine incorporation was seen which was similar to the maximal effect of IGF-I. These [3H]thymidine incorporation results were corroborated with cell replication studies. MC-51, a highly specific monoclonal antibody for the insulin receptor, inhibited the stimulation of [3H]thymidine incorporation by 25 ng/ml of insulin. AlphaIR-3, a monoclonal antibody specifically directed against the type I IGF receptor, had no significant effect on insulin-stimulated [3H]thymidine incorporation at low (10-1000 ng/ml) concentrations of insulin. However, alphaIR-3 interfered with the incremental increase in [3H]thymidine incorporation observed at 10-100 μg/ml insulin. These data demonstrate that insulin, at low concentrations, is capable of stimulating DNA synthesis and replication of human fibroblasts through interaction with its own receptor, while at supraphysiological concentrations, much of insulin's mitogenic effect is mediated through the type I IGF receptor.",
author = "A. Conover and Hintz, {R. L.} and Rosenfeld, {Ronald (Ron)}",
year = "1989",
language = "English (US)",
volume = "21",
pages = "59--63",
journal = "Hormone and Metabolic Research",
issn = "0018-5043",
publisher = "Georg Thieme Verlag",
number = "2",

}

TY - JOUR

T1 - Direct evidence that the insulin receptor mediates a mitogenic response in cultured human fibroblasts

AU - Conover, A.

AU - Hintz, R. L.

AU - Rosenfeld, Ronald (Ron)

PY - 1989

Y1 - 1989

N2 - To define the role of the insulin receptor in mediating a mitogenic response in cultured human fibroblasts, the effects of specific monoclonal antibodies against the insulin and the type I IGF receptor on insulin-stimulated [3H]thymidine incorporation were investigated. Insulin stimulated [3H]thymidine incorporation in a biphasic fashion. In the first phase, a half-maximal effect was observed at 20 ng/ml, and a seemingly maximal effect was obtained at 100-1000 ng/ml. With 10 μg/ml insulin, a secondary increase in [3H]thymidine incorporation was seen which was similar to the maximal effect of IGF-I. These [3H]thymidine incorporation results were corroborated with cell replication studies. MC-51, a highly specific monoclonal antibody for the insulin receptor, inhibited the stimulation of [3H]thymidine incorporation by 25 ng/ml of insulin. AlphaIR-3, a monoclonal antibody specifically directed against the type I IGF receptor, had no significant effect on insulin-stimulated [3H]thymidine incorporation at low (10-1000 ng/ml) concentrations of insulin. However, alphaIR-3 interfered with the incremental increase in [3H]thymidine incorporation observed at 10-100 μg/ml insulin. These data demonstrate that insulin, at low concentrations, is capable of stimulating DNA synthesis and replication of human fibroblasts through interaction with its own receptor, while at supraphysiological concentrations, much of insulin's mitogenic effect is mediated through the type I IGF receptor.

AB - To define the role of the insulin receptor in mediating a mitogenic response in cultured human fibroblasts, the effects of specific monoclonal antibodies against the insulin and the type I IGF receptor on insulin-stimulated [3H]thymidine incorporation were investigated. Insulin stimulated [3H]thymidine incorporation in a biphasic fashion. In the first phase, a half-maximal effect was observed at 20 ng/ml, and a seemingly maximal effect was obtained at 100-1000 ng/ml. With 10 μg/ml insulin, a secondary increase in [3H]thymidine incorporation was seen which was similar to the maximal effect of IGF-I. These [3H]thymidine incorporation results were corroborated with cell replication studies. MC-51, a highly specific monoclonal antibody for the insulin receptor, inhibited the stimulation of [3H]thymidine incorporation by 25 ng/ml of insulin. AlphaIR-3, a monoclonal antibody specifically directed against the type I IGF receptor, had no significant effect on insulin-stimulated [3H]thymidine incorporation at low (10-1000 ng/ml) concentrations of insulin. However, alphaIR-3 interfered with the incremental increase in [3H]thymidine incorporation observed at 10-100 μg/ml insulin. These data demonstrate that insulin, at low concentrations, is capable of stimulating DNA synthesis and replication of human fibroblasts through interaction with its own receptor, while at supraphysiological concentrations, much of insulin's mitogenic effect is mediated through the type I IGF receptor.

UR - http://www.scopus.com/inward/record.url?scp=0024603824&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024603824&partnerID=8YFLogxK

M3 - Article

C2 - 2722129

AN - SCOPUS:0024603824

VL - 21

SP - 59

EP - 63

JO - Hormone and Metabolic Research

JF - Hormone and Metabolic Research

SN - 0018-5043

IS - 2

ER -