Leucine suppresses glucose absorption with concomitant modulation of metabolic activities linked to postprandial hyperglycemia in jejunums of isolated rats’ small intestines

Purpose: Postprandial hyperglycemia arising from increased intestinal glucose absorption has been implicated in the pathophysiology of diabetes mellitus. The present study investigated the inhibitory activity of leucine on intestinal glucose absorption and its effect on glucose metabolism, redox imbalance, cholinergic and purinergic homeostasis in jejunums of isolated rats’ small intestines. Methods: Isolated jejunum was incubated with different concentrations (30–240 μg/mL) of leucine in the presence of 11.1 mM glucose for 2 h at 37 °C. Negative control consisted of jejunums incubated with only glucose, while incubation with no glucose and/or leucine served as normal control. Acarbose was used as the standard antidiabetic drug. Results: Incubation of jejunum with glucose significantly elevated intestinal glucose absorption with concomitant depletion in glutathione level, superoxide dismutase, catalase, and ATPase activities. It also significantly elevated malondialdehyde level, acetylcholinesterase, ENTPDase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase, and amylase activities. These levels and activities were significantly reversed in jejunums incubated with leucine. In silico studies further revealed potent molecular interaction of leucine with SGLT1 and GLUT2. Conclusion: These results indicate that leucine inhibition of intestinal glucose absorption involves mitigation of intestinal oxidative stress and cholinergic dysfunction, with concomitant modulation of intestinal purinergic and glucogenic activities. These suggests leucine to be a potent nutraceutical in the management of postprandial hyperglycemia in diabetics.