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-microM concentration, the meglitinide analogue caused a modest increase in 14CO2 output from islets prelabeled with L-[U-14C]glutamine but failed to affect D-[5-3H]glucose utilization, D-[U-14C]glucose oxidation and conversion into 14C-labeled acidic metabolites and amino acids, L[1-14C]leucine and L-[U-14C]leucine oxidation, the generation of 2-ketoisocaproate and further acidic metabolites from the branched-chain amino acid and the production of 14CO2 by islets prelabeled with [U-14C]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.
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
W J
WJ
Malaisse
A
A
Sener
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D000077715:Nateglinide; D010084:Oxidation-Reduction / Q000187:drug effects; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D001549:Benzamides; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D000077715:Nateglinide; D010649:Phenylalanine; C030516:meglitinide; D007930:Leucine; D005947:Glucose