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Mitogen-activated protein kinases as glucose transducers for diabetic complications

D R Tomlinson1

  • 1Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, UK.

Diabetologia
|November 7, 1999
PubMed

Insights

High glucose levels damage cells through pathways like the sorbitol pathway and oxidative stress, activating mitogen-activated protein kinases (MAP kinases). Targeting these MAP kinases may offer therapeutic control for diabetic complications.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Diabetic complications arise from glucose-induced cellular damage, with mechanisms including the sorbitol pathway, protein glycation, and oxidative stress.
  • These pathways are interconnected and contribute to hyperglycaemia-associated biochemical anomalies.

Purpose of the Study:

  • To explore the role of mitogen-activated protein kinases (MAP kinases) as central mediators of glucose-induced cellular damage.
  • To investigate the link between protein kinase C (PKC) activation and MAP kinase signaling in diabetic complications.

Main Methods:

  • Review of existing hypotheses on glucose toxicity in diabetes.
  • Analysis of the interconnectedness of biochemical pathways activated by hyperglycaemia.
  • Examination of the role of MAP kinases and PKC in cellular signaling.

Main Results:

  • Mitogen-activated protein kinases (MAP kinases) are proposed as glucose transducers, activated by hyperglycaemia-related pathways.
  • Protein kinase C (PKC) activation, implicated in retinopathy and neuropathy, effectively activates MAP kinases.
  • MAP kinases phosphorylate transcription factors, altering gene expression, cellular phenotype, and extracellular matrix production.

Conclusions:

  • Mitogen-activated protein kinases (MAP kinases) can initiate cellular events leading to diabetic nephropathy, retinopathy, and neuropathy.
  • Pharmacological modulation of MAP kinases presents a potential therapeutic strategy for managing diabetic complications.

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