The evolutionary benefit of insulin resistance

M.R. Soeters, P.B. Soeters

Research output: Contribution to journalArticleAcademicpeer-review

40 Citations (Scopus)

Abstract

Insulin resistance is perceived as deleterious, associated with conditions as the metabolic syndrome, type 2 diabetes mellitus and critical illness. However, insulin resistance is evolutionarily well preserved and its persistence suggests that it benefits survival. Insulin resistance is important in various states such as starvation, immune activation, growth and cancer, to spare glucose for different biosynthetic purposes such as the production of NADPH, nucleotides in the pentose phosphate pathway and oxaloacetate for anaplerosis. In these conditions, total glucose oxidation by the tricarboxylic acid cycle is actually low and energy demands are largely met by fatty acid and ketone body oxidation. This beneficial role of insulin resistance has consequences for treatment and research. Insulin resistance should be investigated at the cellular, tissue and whole organism level. The metabolic pathways discussed here, should be integrated in the accepted and valid mechanistic events of insulin resistance before interfering with them to promote insulin sensitivity at any cost.
Original languageEnglish
Pages (from-to)1002-1007
Number of pages6
JournalClinical Nutrition
Volume31
Issue number6
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Insulin resistance
  • Pentose phosphate pathway
  • Protein
  • Obesity
  • Diabetes
  • Starvation
  • Growth
  • Immune activation
  • PENTOSE-PHOSPHATE PATHWAY
  • BETA-CELL FUNCTION
  • GLUCOSE-METABOLISM
  • SKELETAL-MUSCLE
  • MITOCHONDRIAL DYSFUNCTION
  • PARENTERAL-NUTRITION
  • ACID OXIDATION
  • GLUCONEOGENESIS
  • AMINO
  • MECHANISMS

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