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Molecular mechanisms of insulin resistance in type 2 diabetes mellitus

Vandana Saini1

  • 1Vandana Saini, Department of Biochemistry, Lady Hardinge Medical College, New Delhi 110001, India.

World Journal of Diabetes
|May 4, 2011
PubMed

Insights

Free fatty acids impair insulin sensitivity in type 2 diabetes by disrupting insulin signaling pathways. Understanding these mechanisms offers new therapeutic targets for diabetes treatment and prevention.

Area of Science:

  • Metabolic diseases
  • Endocrinology
  • Molecular biology

Background:

  • Free fatty acids are implicated in type 2 diabetes mellitus (T2DM)-related insulin resistance.
  • The precise molecular mechanisms underlying this phenomenon remain incompletely understood.
  • Adipokines from adipose tissue also influence tissue response to insulin.

Purpose of the Study:

  • To summarize current understanding of insulin resistance pathophysiology in T2DM.
  • To identify potential novel therapeutic targets for T2DM treatment and prevention.

Main Methods:

  • Review of existing literature on insulin resistance in T2DM.
  • Analysis of molecular pathways involving free fatty acids, adipokines, and intracellular signaling molecules.
  • Examination of genetic and cellular studies investigating key proteins.

Main Results:

  • Increased intracellular fatty acid metabolites may activate serine kinases, impairing insulin receptor signaling.
  • Dysfunction of insulin receptor substrate-2, protein kinase B, and forkhead transcription factor Foxo 1a contributes to insulin resistance.
  • Phosphorylation of protein kinase Cε and mitochondrial dysfunction are implicated in reduced insulin receptor gene expression and weakened insulin signaling.

Conclusions:

  • Insulin resistance in T2DM involves complex molecular disruptions.
  • Key proteins and pathways identified present potential targets for therapeutic intervention.
  • Further research into these mechanisms could lead to effective T2DM prevention and treatment strategies.
Keywords:
AdipokinesForkhead box protein OInsulin receptorInsulin receptor substrate proteinsInsulin resistanceInsulin signalingPhosphatidylinositol 3-kinaseProtein kinase BType 2 diabetes mellitus

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