OMMITTEE CHAIR: Dr. Kazeem Olanrewaju

TITLE: DEVELOPMENT OF A COMPARTMENTAL METABOLISM RATE MODEL FOR DIGESTIVE OLIGOSACCHARIDES TRANSFORMATION TO GLUCOSE IN THE HUMAN PROXIMAL SMALL INTESTINE (PSI)

ABSTRACT: Excess postprandial glucose remains a significant metabolic concern, particularly for individuals with impaired glucose regulation. In the proximal small intestine (PSI), dietary oligosaccharides are enzymatically hydrolyzed to glucose, which is subsequently absorbed into the bloodstream. However, direct measurement of these coupled digestion–absorption processes in vivo is limited, making in silico mechanistic modeling a practical approach for analyzing system behavior under controlled conditions. In this work, a time-dependent compartmental model is developed to describe oligosaccharide/starch hydrolysis and glucose absorption in the PSI. The intestine is represented as a series of continuous stirred-tank reactor (CSTR) segments, where each segment captures temporal concentration changes, and inter-segment flow represents forward transport. As opposed to past works, the formulation does not assume tubular or plug-flow behavior; instead, spatial trends emerge implicitly through the sequence of compartments. Three complementary models are proposed. With kinetic parameters from literature data, Model 1 assumes steady continuous inflow and provides an idealized baseline for evaluating how species concentrations evolve from one segment to the next. Although Model 1 is not strictly physiological, it offers a valid reference and foundational case for isolating the effect of flow dynamics on digestion behavior. Model 2 introduces pulsatile inflow to represent intermittent gastric emptying, producing transient concentration spikes. Model 3 serves as the primary framework and incorporates Michaelis-Menten kinetics for glucose formation and absorption, with intermittent gastric emptying representing average physiological inflow. A sub-model (Model 3A) further resolves the pathway from oligosaccharides to maltose and ultimately glucose, allowing intermediate species to be examined. Together, the models complement each other by separating kinetic effects from inflow dynamics, providing a structured framework for analyzing digestion behavior. Simulation results show that oligosaccharides are rapidly hydrolyzed in proximal segments, with intermediates appearing transiently before conversion to glucose. Glucose accumulation is limited due to efficient absorption, resulting in low concentrations in distal segments. A key finding is that gastric emptying patterns strongly influence glucose profiles: pulsatile inflow leads to sharp concentration peaks, whereas continuous inflow produces smoother distributions. Across all models, hydrolysis occurs predominantly in early segments, while absorption dominates glucose removal. Overall, the developed modeling framework provides a mechanistic and interpretable approach for analyzing carbohydrate digestion in the proximal small intestine. Rather than replacing experimental studies, it serves as a structured and practical alternative for studying system behavior under controlled conditions, testing hypotheses, and identifying dominant mechanisms that are otherwise difficult to isolate experimentally. The findings from this work demonstrate that oligosaccharide hydrolysis occurs predominantly in proximal regions, that glucose absorption rapidly limits its accumulation, and that gastric emptying patterns play a critical role in shaping glucose concentration profiles. This also serves as a platform that can potentially support efforts to optimize glucose in the human body and ultimately proffer better treatment solutions for diabetes and liver-related diseases.

Keywords: Carbohydrate digestion, compartmental modeling, gastric emptying dynamics, glucose absorption kinetics, proximal small intestine.

Room Location: Chemical Engineering Conference Room (ROOM 200 C. L. Wilson Engineering Building)