Metabolic changes in the midgut of Eri silkworm after Oral administration of 1-deoxynojirimycin: A 1H-NMR-based metabonomic study

Abstract

1-deoxynojirimycin (DNJ) is a natural D-glucose analogue and has a strong physiological activity in inhibiting α-glucosidase in vivo. The antidiabetic effects of DNJ in mice or other mammals were extensively explored, but the physiological and toxic roles of DNJ in insects was seldom reported. In this study, the biological effects of DNJ were examined in midgut extracts of fourth-instar larvae of Eri silkworm (Samia cynthia ricini, Saturniidae). Based on nuclear magnetic resonance (NMR) metabonomics technology, we analyzed the alterations of glycometabolism, lipids, and energy metabolism pathways in the midgut of S. cynthia ricini caused by DNJ. Pattern recognition analysis (partial least square-discriminant analysis, PLS-DA) showed that four groups of latex, 0.25% DNJ, 0.5% DNJ and the mixture of 0.5% DNJ and latex (1:1) were distinctly different from the control group. Moreover, several metabolic pathways of DNJ-mediated modulation in the midgut were identified. Compared with the control group, alanine, succinate, glutamate, and fumarate concentrations decreased in three groups of 0.5% DNJ, latex, and the mixture, choline levels increased in two DNJ groups, and trehalose levels increased in all experimental groups. Therefore, these results suggest that DNJ modulated lipid metabolism by limiting the hydrolysis pathways of phospholipids metabolism. Additionally, DNJ has a potent negative effect on energy metabolism by inhibiting the hydrolysis of trehalose, glycolysis and the tricarboxylic acid (TCA) cycle. Overall, DNJ, as a single-ingredient, is an efficient substance for modulating lipid metabolism and inhibiting energy metabolism.

Comparative transcriptome analysis reveals significant metabolic alterations in eri-silkworm (Samia cynthia ricini) haemolymph in response to 1-deoxynojirimycin

“…Glycometabolism plays an important role in the physiological balance of living organisms [ 27 ]. As shown in our previous studies, the glycometabolism pathway was impaired in the haemolymph and midgut of fourth-instar larvae after oral administration of DNJ [ 18 , 19 ]. In this study, based on the KEGG database analyses, the up-regulated genes related to glycometabolism were mainly enriched in N-glycan biosynthesis, glycolysis and gluconeogenesis, starch and sucrose metabolism, and the down-regulated genes associated with glycometabolism were mainly enriched in fructose and mannose metabolism.…”

“…As an alkaloid from mulberry, DNJ shows substantial inhibitory activity towards α-glucosidase in vitro , which may be beneficial for suppressing abnormally high blood glucose levels [ 3 ]. In our previous study, we used eri-silkworm as a model to study the toxic actions of DNJ via metabonomics, and DNJ modulated glycometabolism and inhibit glucogenesis and energy metabolism [ 18 , 19 ]. DNJ is reported to exert a significant inhibitory effect on the activity of α-glucosidase.…”

“…An insect that consumes a high sugar or high fat food for a long period will display disturbances in fat metabolism and lipotoxicity in organs [ 40 ]. DNJ has been shown to modulate lipid metabolism and prevent hyperlipidaemia [ 9 , 19 , 41 , 42 ]. In the present study, most of the genes involved in lipid metabolism were up-regulated after treatment with DNJ.…”

“…As shown in our previous study, DNJ has a positive impact on reverse glycometabolism by modulating glycometabolism and inhibiting glucogenesis and energy metabolism in the fourth-instar eri-silkworm haemolymph [ 18 ]. In the eri-silkworm midgut, DNJ not only exerts a potent negative effect on energy metabolism and glycometabolism but also modulates lipid metabolism [ 19 ]. However, the metabolic mechanism underlying the fifth-instar eri-silkworm response to DNJ is unclear, particularly at the transcriptional level.…”

Mode of Action of Anti-diabetic Phyto-Compounds Present in Traditional Indian Plants: A Review

“…The main active ingredients apart from DNJ, in mulberry leaves, are flavones, polysaccharides, and alkaloids. The hypoglycemic effect of alkaloids is due to polyhydroxy alkaloids, known as α inhibitors which inhibit the α-glucosidase in the small intestine [69,70]. Hot water extract of mulberry leaves have shown a significant inhibitory effect against α-glucosidases, sucrase and maltase enzymes in Caco-2 cell culture and considered to have the potential to be consumed as antidiabetic herb tea [62].…”