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Hexosamines and insulin resistance

D A McClain1, E D Crook

  • 1Veterans Administration Medical Center, Jackson, Mississippi. dam@fiona.umsmed.edu

Diabetes
|August 1, 1996
PubMed
Summary
This summary is machine-generated.

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The hexosamine biosynthesis pathway regulates glucose metabolism and may cause insulin resistance when overactive. Its rate-limiting enzyme activity correlates with glucose disposal rates, suggesting a key role in glucose homeostasis.

Area of Science:

  • Biochemistry
  • Cellular Metabolism
  • Endocrinology

Background:

  • Glucose is a critical regulator of cell growth and metabolism.
  • Hyperglycemia's adverse effects may stem from abnormal glucose concentrations impacting normal regulatory processes.
  • The precise mechanism by which cells sense glucose remains incompletely understood.

Purpose of the Study:

  • To investigate the role of the hexosamine biosynthesis pathway in cellular glucose sensing and regulation.
  • To explore the connection between hexosamine pathway flux and insulin resistance.
  • To examine the correlation between the activity of glutamine:fructose-6-phosphate amidotransferase and glucose disposal rates.

Main Methods:

  • Assessing the impact of hexosamine pathway flux on glucose uptake, glycogen synthesis, and glycolysis in various models.

Related Experiment Videos

  • Inducing excess hexosamine flux in cultured cells, tissues, and animals to evaluate insulin resistance.
  • Measuring the activity of glutamine:fructose-6-phosphate amidotransferase and correlating it with glucose disposal rates in humans and transgenic mice.

    • Main Results:

    • Evidence suggests the hexosamine biosynthesis pathway regulates glucose uptake, glycogen synthesis, glycolysis, and growth factor synthesis.
    • Excessive hexosamine flux leads to insulin resistance in cellular, tissue, and animal models.
    • Activity of glutamine:fructose-6-phosphate amidotransferase correlates with glucose disposal rates in normal humans and transgenic mice.

    Conclusions:

    • The hexosamine biosynthesis pathway is implicated as a key cellular glucose sensor.
    • Dysregulation of the hexosamine pathway, particularly excess flux, contributes to insulin resistance.
    • The rate-limiting enzyme of hexosamine synthesis is a potential biomarker for glucose homeostasis and related diseases.