L-leucine and a nonmetabolized analogue activate pancreatic islet glutamate dehydrogenase

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Abstract
The release of insulin evoked by nutrients in the pancreatic β-cell is attributed to either the activation of a stereospecific receptor by the nutrient molecule itself or the generation of one or more signal(s) through the intracellular metabolism of the nutrient secretagogue1. The first of these hypotheses is apparently supported by the fact that nonmetabolized amino acids, especially the L-leucine analogue b(−)2-aminobicyclo[2,2, 1]heptane-2-carbocyclic acid (BCH), stimulate insulin release2. However, we now report evidence in support of the second hypothesis. We present data consistent with the idea that BCH induces insulin release through the allosteric activation of glutamate dehydrogenase. This is compatible with the fuel hypothesis, which states that the secretory response to nutrient secretagogues depends always on an increase of catabolic fluxes in the islet cells3,4.