Effect of N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine on nutrient catabolism in rat pancreatic islets

1. The effect of N-[(trans-4-isopropylcyclohexyl]-carbonyl)-D-phenylalanine (A-4166) on nutrient metabolism was investigated in isolated rat pancreatic islets. 2. At a 10-mu M concentration, the meglitinide analogue caused a modest increase in (CO2)-C-14 output from islets prelabeled with L-[U-C-14]glutamine but failed to affect D-[5-H-3]glucose utilization, D-[U-C-14]glucose oxidation and conversion into C-14-labeled acidic metabolites and amino acids, L[1-C-14]leucine and L-[U-C-14]leucine oxidation, the generation of 2-ketoisocaproate and further acidic metabolites from the branched chain amino acid and the production of (CO2)-C-14 by islets prelabeled with [U-C-14]palmitate. 3. These findings indicate that the insulinotropic action of A-4166 is not attributable to any sizeable increase in the metabolism of exogenous or endogenous nutrients. (C) 1998 Elsevier Science Inc.