Insulin action impaired by deficiency of the G-protein subunit G ialpha2

Nature. 1996 Feb 29;379(6568):840-4. doi: 10.1038/379840a0.


Integration of information between tyrosine kinase and G-protein-mediated pathways is necessary, but remains poorly understood. Here we use cells from transgenic mice harbouring inducible expression of RNA antisense to the gene encoding G ialpha2 to show that G ialpha2 is critical for insulin action. G ialpha2 deficiency in adipose tissue and liver produces hyperinsulinaemia, impaired glucose tolerance and resistance to insulin in vivo. Insulin resistance affects glucose-transporter activity and recruitment, counterregulation of lipolysis, and activation of glycogen synthase, all of which are cardinal responses to insulin. G ialpha2 deficiency increases protein-tyrosine phosphatase activity and attenuates insulin-stimulated tyrosine phosphorylation of IRS (insulin-receptor substrate 1) in vivo. G ialpha2 deficiency creates a model for insulin resistance characteristic of noninsulin-dependent diabetes mellitus (NIDDM), implicating G ialpha2 as a positive regulator of insulin action.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Biological Transport
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Disease Models, Animal
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / deficiency
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / physiology*
  • Glucose Transporter Type 4
  • Glycogen Synthase / metabolism
  • Hyperinsulinism / metabolism
  • Insulin / physiology*
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance
  • Lipolysis
  • Liver / metabolism
  • Mice
  • Mice, Transgenic
  • Monosaccharide Transport Proteins / metabolism
  • Muscle Proteins*
  • Phosphoproteins / metabolism
  • RNA, Antisense / genetics


  • Blood Glucose
  • Glucose Transporter Type 4
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Phosphoproteins
  • RNA, Antisense
  • Slc2a4 protein, mouse
  • Glycogen Synthase
  • GTP-Binding Proteins