The stimulus-secretion coupling of amino acid-induced insulin release: insulinotropic action of branched-chain amino acids at physiological concentrations of glucose and glutamine

Eur J Clin Invest. 1981 Dec;11(6):455-60. doi: 10.1111/j.1365-2362.1981.tb02013.x.


The stimulant action of branched-chain amino acids upon insulin release was examined in rat pancreatic islets incubated at physiological concentrations of D-glucose and L-glutamine. In the presence of the latter nutrients, L-leucine and L-isoleucine used together at a physiological concentration (0.25 mmol/l each) doubled insulin secretion rate. The effect of L-leucine upon insulin release was dose-related without any indication of of a threshold phenomenon. The insulinotropic action of L-leucine was mimicked, to a limited extent, by its nonmetabolized analogue, 2-aminobicyclo[2,2,1] heptane-2-carboxylic acid. L-Glutamine slightly inhibited glucose-stimulated insulin release. It is concluded that, under close-to-physiological conditions, L-leucine stimulates insulin release by acting in the islet cells both as a fuel and as an allosteric activator of glutamate dehydrogenase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology
  • Amino Acids, Cyclic*
  • Animals
  • Culture Media
  • Enzyme Activation
  • Glucose / pharmacology
  • Glutamate Dehydrogenase / metabolism
  • Glutamine / pharmacology
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Isoleucine / pharmacology*
  • Leucine / pharmacology*
  • Rats
  • Stimulation, Chemical


  • Amino Acids
  • Amino Acids, Cyclic
  • Culture Media
  • Insulin
  • Isoleucine
  • Glutamine
  • 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid
  • Glutamate Dehydrogenase
  • Leucine
  • Glucose