Discussion
glucotoxicity, T2D
SECONDARY, DEPOLARIZATION, PATHOGENESIS
The present study investigated the effects of an acute dose of pre-meal WP (15 g) on pancreatic β-cell function and postprandial insulin kinetics, and their subsequent influence on PPG excursions in people with T2D. Our primary finding is that, at the whole-body level, pre-meal WP integrates a reciprocal mechanism that involves an enhancement in β-cell function with a reduction in insulin clearance (MCRi). This produces an effective plasma insulin profile to rising glucose concentrations without requiring further β-cell stimulation and insulin release.We confirm prior reports demonstrating that a low dose of pre-meal WP reduces PPG excursions in people with T2D (Despite enhancing β-cell function, overall insulin secretion was unaffected by our WP preload. Instead, our data indicate that pre-meal WP affects insulin kinetics, namely by reducing MCRi. This observation was intriguing, particularly since the decline in postprandial insulin clearance appears blunted in T2D (Our findings concerning the role of MCRi and ISR on PPG homeostasis following a WP preload are novel and may be of interest in the pathogenesis of T2D. As was demonstrated here, for individuals with compromised β-cell function, a reduction in postprandial MCRi enabled an appropriate insulin profile to be achieved without placing further stress on the β-cells for insulin release. This subsequently resulted in a 16% reduction in PPG iAUC, which may concomitantly improve β-cell viability through a reduction in glucotoxicity within the β-cell (While the mechanism(s) explaining the observed reduction in MCRi are unclear, explorative analysis highlighted an inverse relationship between glucagon iAUCAs anticipated, pre-meal WP augmented the early and sustained increase in GLP-1 secretion, which most likely reflects the rapid delivery of amino acids to the small intestine and the subsequent depolarization of the enteroendocrine L-cell (Strengths associated with our study include the randomized, placebo-controlled design and counterbalanced administration of treatments. Moreover, prehepatic ISR were calculated, thus circumventing interindividual hepatic and posthepatic insulin extraction. We also used a conventional mixed-nutrient meal to convey the expected islet and gastrointestinal responses to the ingestion of a commonly consumed meal, thereby increasing the real-world validity of our findings. Similarly, we chose to present our pre-meal shots at a time that was deemed more likely to embody free-living eating patterns. Nevertheless, it must be recognized that the reported data were secondary outcomes from our primary study (In summary, the ingestion of a low dose of pre-meal WP reduces PPG excursions in adults with T2D by coordinating an enhancement in β-cell function with a reduction in MCRi to produce an efficient plasma insulin profile. The reduction in insulin clearance may represent a counterregulatory response to an increase in glucagon signaling and hepatic glucose output. Studies tracing PPG fluxes with appropriate methodology following pre-meal WP warrant future evaluation.