Blood sugar formation due to abnormally elevated gluconeogenesis: aberrantregulation in a parasitized insect, Manduca sexta Linnaeus

Alterations of carbohydrate metabolism associated with parasitism were exam ined in an insect, Manduca sexta L. In insect larvae maintained on a low ca rbohydrate diet gluconeogenesis from [3-C-13]alanine was established from t he fractional C-13 enrichment in trehalose, a disaccharide of glucose and t he blood sugar of insects and other invertebrates. After transamination of the isotopically substituted substrate to [3-C-13]pyruvate, the latter was carboxylated to oxaloacetate ultimately leading to de novo glucose synthesi s and trehalose formation. Trehalose was selectively enriched with C-13 at C1 and C6 followed by C2 and C5. C-13 enrichment of blood sugar in insects parasitized by Cotesia congregata (Say) was significantly greater than was observed in normal animals. The relative contributions of pyruvate carboxyl ation and decarboxylation to trehalose labeling were determined from the C- 13 distribution in glutamine, synthesized as a byproduct of the tricarboxyl ic acid cycle. The relative contribution of carboxylation was significantly greater in parasitized larvae than in normal insects providing additional evidence of elevated gluconeogenesis due to parasitism. Despite the increas ed gluconeogenesis in parasitized insects the level of blood sugar was the same in all animals. Because de novo glucose synthesis does not normally ma intain blood sugar level in insects maintained under these dietary conditio ns the findings suggest an aberrant regulation over gluconeogenesis. The C- 13 labeling in trehalose was nearly symmetric in all insects but the mean C 1/C6 C-13 ratio was higher in parasitized animals suggesting a lower activi ty of the pentose phosphate pathway that brings about a redistribution of C -13 in trehalose following de novo glucose synthesis. Additional studies wi th insects maintained on a high carbohydrate diet and administered [1,2-C-1 3(2)]glucose confirmed a decreased level of pentose cycling during parasiti sm consistent with a lower level of lipogenesis. It is suggested, however, that the pentose pathway may facilitate the synthesis of trehalose from die tary carbohydrate by directing hexose phosphate cycled through the pathway to the production of energy. (C) 1999 Elsevier Science B.V. All rights rese rved.