This study compared the acute effects of orally administered L‑Serine (L‑Ser) and D‑Serine (D‑Ser) on postprandial blood glucose regulation in healthy C57BL/6J mice. The work examined glucose responses after a single dose given at the time of glucose loading and investigated mechanisms focusing on intestinal glucose handling and transporter expression.
Healthy C57BL/6J mice were used to evaluate acute glucose responses. Oral glucose tolerance tests (OGTTs) were performed with simultaneous administration of either L‑Ser or D‑Ser at 2.0 g/kg body weight together with the glucose load. Additional experiments included insulin tolerance tests (ITTs), intraperitoneal glucose tolerance tests (IPGTTs), ex vivo intestinal absorption assays using everted intestine, and Western blot analysis of intestinal brush border membrane proteins.
When administered orally at the time of glucose loading, both L‑Ser and D‑Ser significantly suppressed postprandial hyperglycemia compared with control mice that received glucose alone. The suppression of blood glucose occurred acutely after a single oral dose, indicating an immediate effect on the postprandial glycemic excursion in this healthy mouse model.
Serum insulin measurements after glucose loading showed no significant differences between groups treated with L‑Ser, D‑Ser, and control. Similarly, insulin tolerance tests did not reveal significant changes in systemic insulin sensitivity after administration of either enantiomer. These findings indicate that the glucose‑lowering effects observed were not mediated by increased insulin secretion or improved insulin sensitivity in these acute experiments.
Intraperitoneal glucose tolerance tests were conducted to probe whether L‑Ser or D‑Ser affects systemic glucose handling independent of the intestinal route. IPGTTs showed no significant changes in postprandial hyperglycemia after administration of either L‑Ser or D‑Ser. The lack of effect after intraperitoneal glucose delivery supports a mechanism localized to the gastrointestinal tract rather than a direct systemic modulation of glucose disposal.
To directly assess intestinal glucose uptake, the investigators used an everted intestine assay. Both L‑Serine and D‑Serine significantly suppressed glucose absorption in this ex vivo preparation. The everted intestine results provide functional evidence that the oral administration of these amino acid enantiomers reduces intestinal uptake of glucose, consistent with the observed reductions in postprandial blood glucose after oral glucose loading.
Western blotting analysis of brush border membrane preparations was used to evaluate the expression of major intestinal glucose transporters. Results differed by stereochemistry: L‑Serine reduced expression of GLUT2, whereas D‑Serine reduced expression of both SGLT1 and GLUT2. These distinct patterns suggest stereospecific regulation of transporter proteins that mediate intestinal glucose absorption.
Collectively, the data indicate that single oral administration of L‑Ser and D‑Ser acutely suppresses postprandial hyperglycemia in healthy mice by inhibiting intestinal glucose absorption. The effect appears to be independent of changes in insulin secretion or systemic insulin sensitivity, and is specific to oral (intestinal) glucose delivery as intraperitoneal glucose responses were unchanged. Differences in the impact on transporter expression—L‑Ser reducing GLUT2 and D‑Ser reducing both SGLT1 and GLUT2—point to stereospecific mechanisms affecting intestinal glucose transport.
The authors highlighted key terms including glucose transporters, intestinal glucose absorption, and postprandial hyperglycemia, and noted stereospecific regulation by L‑ and D‑enantiomers of serine. The study was performed in healthy mice; the abstract does not report dose‑response curves beyond the single tested dose, long‑term administration data in this work, or direct translational data in humans.
(Details such as numerical values for glucose reduction, exact time points, sample sizes, and full methodological parameters were not reported in the abstract provided.)