High glucose concentration decreases insulin-like growth factor type 1-mediated mitogen-activated protein kinase activation in bovine retinal endothelial cells

Vikki Anne McBain, Marie Robertson, Elizabeth Muckersie, John Vincent Forrester, R. M. Knott

Research output: Contribution to journalArticle

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Abstract

Clinical trials have incontrovertibly demonstrated that the onset and progression of diabetic retinopathy (DR) is influenced by the control of glucose levels in patients. In the present study, we examined the effect of glucose concentration on the responsiveness of bovine retinal endothelial cells (BREC) to insulin-like growth factor type 1 (IGF-1). Retinal endothelial cells were isolated from bovine retina and cultured in 5 or 20 mmol/L glucose with or without 100 ng/mL IGF-1. The level of cell growth and p42/44 and p38 mitogen-activated protein kinase (MAPK) activation was determined using the alamarBlue (Serotech) assay and Western blotting, respectively. IGF-1 significantly enhanced cell growth in BREC exposed to 5 mmol/L glucose but not in cells exposed to high glucose concentrations (20 mmol/L). IGF-1 induced a transient activation of p42/44 MAPK, with peak activation at 15 minutes in cells exposed to 5 mmol/L glucose; however, no increase in p42/44 MAPK was evident at the higher glucose concentration of 20 mmol/L. There was no significant change in the level of p38 MAPK during the time period examined when IGF-1 was also present. However, high glucose concentrations alone increased the level of p38 MAPK after 60 minutes and the level of p42/44 MAPK after only 15 minutes exposure in 20 mmol/L glucose. Thus, BREC exposed to high glucose concentrations are not sensitive to IGF-1 and this is due, at least in part, to a reduced activation of the p42/44 MAPK pathway. Furthermore, the presence of IGF-1 appears to exert a protective effect on the cells in high glucose concentration by preventing progression through the cell cycle. (C) 2003 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)547-551
Number of pages4
JournalMetabolism
Volume52
Issue number5
DOIs
Publication statusPublished - 2003

Keywords

  • GLOMERULAR MESANGIAL CELLS
  • FACTOR-I
  • INDUCED PROLIFERATION
  • DIABETIC-RETINOPATHY
  • TRANSPORTER
  • RECEPTORS
  • PATHWAYS
  • CULTURE

Cite this

High glucose concentration decreases insulin-like growth factor type 1-mediated mitogen-activated protein kinase activation in bovine retinal endothelial cells. / McBain, Vikki Anne; Robertson, Marie; Muckersie, Elizabeth; Forrester, John Vincent; Knott, R. M.

In: Metabolism, Vol. 52, No. 5, 2003, p. 547-551.

Research output: Contribution to journalArticle

McBain, Vikki Anne ; Robertson, Marie ; Muckersie, Elizabeth ; Forrester, John Vincent ; Knott, R. M. / High glucose concentration decreases insulin-like growth factor type 1-mediated mitogen-activated protein kinase activation in bovine retinal endothelial cells. In: Metabolism. 2003 ; Vol. 52, No. 5. pp. 547-551.
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AU - McBain, Vikki Anne

AU - Robertson, Marie

AU - Muckersie, Elizabeth

AU - Forrester, John Vincent

AU - Knott, R. M.

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AB - Clinical trials have incontrovertibly demonstrated that the onset and progression of diabetic retinopathy (DR) is influenced by the control of glucose levels in patients. In the present study, we examined the effect of glucose concentration on the responsiveness of bovine retinal endothelial cells (BREC) to insulin-like growth factor type 1 (IGF-1). Retinal endothelial cells were isolated from bovine retina and cultured in 5 or 20 mmol/L glucose with or without 100 ng/mL IGF-1. The level of cell growth and p42/44 and p38 mitogen-activated protein kinase (MAPK) activation was determined using the alamarBlue (Serotech) assay and Western blotting, respectively. IGF-1 significantly enhanced cell growth in BREC exposed to 5 mmol/L glucose but not in cells exposed to high glucose concentrations (20 mmol/L). IGF-1 induced a transient activation of p42/44 MAPK, with peak activation at 15 minutes in cells exposed to 5 mmol/L glucose; however, no increase in p42/44 MAPK was evident at the higher glucose concentration of 20 mmol/L. There was no significant change in the level of p38 MAPK during the time period examined when IGF-1 was also present. However, high glucose concentrations alone increased the level of p38 MAPK after 60 minutes and the level of p42/44 MAPK after only 15 minutes exposure in 20 mmol/L glucose. Thus, BREC exposed to high glucose concentrations are not sensitive to IGF-1 and this is due, at least in part, to a reduced activation of the p42/44 MAPK pathway. Furthermore, the presence of IGF-1 appears to exert a protective effect on the cells in high glucose concentration by preventing progression through the cell cycle. (C) 2003 Elsevier Inc. All rights reserved.

KW - GLOMERULAR MESANGIAL CELLS

KW - FACTOR-I

KW - INDUCED PROLIFERATION

KW - DIABETIC-RETINOPATHY

KW - TRANSPORTER

KW - RECEPTORS

KW - PATHWAYS

KW - CULTURE

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DO - 10.1053/meta.2003.50046

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VL - 52

SP - 547

EP - 551

JO - Metabolism

JF - Metabolism

SN - 0026-0495

IS - 5

ER -