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D-glucose and L-leucine metabolism in neonatal and adult cultured rat pancreatic islets

par Boschero, Antonio Carlos;Bordin, Silvana Auxiliadora;Sener, Abdullah ;Malaisse, Willy
Référence Molecular and cellular endocrinology, 73, 1, page (63-71)
Publication Publié, 1990

Article révisé par les pairs

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Résumé :

Neonatal and adult rat islets, cultured for 7-9 days in the presence of 10.5 mM D-glucose, were incubated for 120 min with either D-glucose (2.8 and 16.7 mM) or L-leucine (1.0 and 20.0 mM). The total and anaerobic rates of glycolysis, as judged respectively through the generation of 3H2O from D-[5-3H]glucose and 14C-labelled lactate from D-[3,4-14C]glucose or D-[6-14C]glucose were higher in neonatal than adult islets, but increased to a lesser relative extent in neonatal than adult islets in response to a rise in hexose concentration. The flow through the pentose phosphate pathway, as judged from the difference between D-[1-14C]glucose and D-[6-14C]glucose oxidation was higher in neonatal than adult islets. The flow through the reaction catalyzed by pyruvate dehydrogenase, as judged from the oxidation of D-[3,4-14C]glucose, was lower in neonatal than adult islets incubated in the presence of 16.7 mM (but not in 2.8 mM) D-glucose. The oxidation of acetyl residues relative to their generation rate, as judged from the ratio of D-[6-14C]glucose to D-[3,4-14C]glucose oxidation, was not affected by the hexose concentration whether in neonatal or adult islets, but was about twice higher in the latter than former islets. The rate of D-[6-14C]glucose oxidation was also higher in adult than neonatal islets, especially at the high concentration of D-glucose. In both neonatal and adult iselts, a rise in hexose concentration stimulated preferentially the oxidation of D-[3,4-14C]glucose or D-[6-14C]glucose relative to the utilization of D-[5-3H]glucose. Inversely, the absence of Ca2+ and presence or cycloheximide inhibited preferentially D-[6-14C]glucose oxidation relative to D-[5-3H]glucose utilization. Such a preferential inhibition was observed both at low and high concentrations of D-glucose in neonatal islets, but only at the high hexose concentration in adult islets. The generation of 14C-labelled acidic metabolites and 14CO2 from L-[U-14C]leucine was higher in neonatal than adult islets exposed to a low concentration of the amino acid. However, a rise in L-leucine concentration increased its catabolism to a lesser extent in neonatal than adult islets. The absence of Ca2+ and presence of cycloheximide again caused a preferential inhibition of L-[U-14C]leucine oxidation relative to its conversion to acidic metabolites in neonatal islets incubated at low or high concentration of L-leucine, but only exerted a comparable effect in adult islets exposed to high concentration of the amino acid. These findings suggest that neonatal islets are actively engaged into energy-consuming anabolic processes even when exposed to low concentrations of D-glucose and L-leucine. However, in response to a rise in either D-glucose or L-leucine concentration, the generation of ATP is increased to a lesser extent in neonatal than adult islets, and this may in turn account for a lesser secretory response to these nutrient secretagogues.