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Normal Akt/PKB with reduced PI3K activation in insulin-resistant mice

S T Nadler1, J P Stoehr, M E Rabaglia

  • 1Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

American Journal of Physiology. Endocrinology and Metabolism
|November 10, 2001
PubMed

Insights

New mouse models reveal insulin resistance in adipose tissue, offering insights into type 2 diabetes. These BtB6 mice show impaired glucose uptake, aiding the study of human metabolic disorders.

Area of Science:

  • Metabolic research
  • Diabetes mellitus
  • Animal models

Background:

  • Insulin resistance is a key feature of type 2 diabetes, characterized by impaired glucose uptake.
  • Understanding the molecular defects in insulin resistance is crucial for developing effective treatments.
  • Experimental models that accurately mimic human insulin resistance are vital for research.

Purpose of the Study:

  • To investigate insulin resistance in adipose tissue using a novel mouse model.
  • To characterize the signaling defects associated with insulin resistance in this model.
  • To establish the utility of BtB6 mice for studying human type 2 diabetes.

Main Methods:

  • Crossbreeding of BTBR and C57BL/6J (B6) mouse strains to produce BtB6 offspring.
  • Isolation and analysis of adipocytes from lean, nondiabetic male and female BtB6 mice.
  • Measurement of insulin-stimulated glucose uptake, IRS-1 phosphorylation, and PI3K/Akt activation.

Main Results:

  • BtB6 male mice exhibit insulin resistance in adipose tissue, mirroring human conditions.
  • Adipocytes from insulin-resistant male mice showed a 65% reduction in insulin-stimulated glucose uptake compared to females.
  • Insulin-stimulated IRS-1 phosphorylation and PI3K activation were diminished, but Akt/PKB activation remained normal.

Conclusions:

  • BtB6 mice present a valuable model for studying insulin resistance due to a dissociation between PI3K and Akt/PKB activation.
  • This model can help elucidate the underlying causes of insulin resistance in humans.
  • Further research using this model may lead to new therapeutic strategies for type 2 diabetes.

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