Page 68 - GTM-4-2

Global Translational Medicine Glucosidase and metabolic profiles

as it is transported through specialized monosaccharide downstream improvements in biochemical pathways
transporters (glucose transporter [GLUT] 1, GLUT2, and related to intermediary metabolism and lipogenesis
GLUT5) located along the basolateral epithelial membrane are likely to follow. 13-15 Thus, dietary supplements or
of the brush border in the gut and liver. Unlike glucose, additives that extend the process of luminal digestion of
10
fructose uptake occurs through insulin-independent starches and absorption of simple carbohydrates, thereby
GLUT transporters. In addition, fructose uptake is a delaying the rate of glucose uptake, present an interesting
saturable, rate-limiting process with a more restrictive prospect for modulating downstream physiological
Michaelis-Menten constant for uptake than glucose, events, including their effects on appetite, satiety factors,
thereby delaying and prolonging immediate glycemic plasma insulin activation, and the metabolic effects of
and insulinogenic responses beyond those typically insulin on lipogenesis and cholesterol production. 9-11 The
encountered after a calorically equivalent non-fructose improvements in glycemic responses would likely elicit
carbohydrate meal. Numerous physicochemical factors, favorable changes in other hormonal activities commonly
including diet composition, can also influence interactions associated with glycemic responses, including thyroidal,
with brush border enzymes, affecting the efficiency of sympathetic, and possibly glucocorticoid interactions.
digestive activities. Specifically, dietary fibers, gums, pectin, The insulinogenic actions exert numerous downstream
and plant-derived phytochemicals can protect against effects on key parameters of intermediary metabolism
glycemic excursions by impeding direct access to brush in peripheral tissues, including modulation of glucose
border enzymatic actions. These food constituents can oxidation, protein synthesis and degradation (protein
effectively decrease the rate and efficiency of luminal brush turnover), carbohydrate oxidation and storage, and
border digestion, leading to a corresponding attenuation lipogenesis, all of which are pertinent to this study. 16-18
of glycemic and secondary insulinogenic responses – a Glucose readily enters glycolysis in peripheral tissues,
well-established benefit of dietary fiber content. The providing substrates for glycogen deposition, as well
7
addition of natural and pharmacologic inhibitors of as reducing equivalents for mitochondrial high-energy
α-glucosidase activity can further attenuate insulinogenic phosphate generation. In contrast, fructose, once absorbed
and glycemic responses without compromising the net by liver or intestinal tissues, is converted to fructose-
digestion or absorption of monosaccharides, nutrients, 1-phosphate and adenosine diphosphate, which then
or micronutrients more distally in the gastrointestinal splits into two trioses (dihydroxyacetone phosphate and
tract. 9-12
glyceraldehyde), both of which can serve as preferential
Characteristic of luminal carbohydrate digestive substrates for de novo insulin-stimulated lipogenesis.
17
enzymes, α-glucosidase activity is greatest in the proximal In addition, adenosine diphosphate undergoes further
regions of the upper intestinal tract and decreases degradation to adenosine monophosphate and inosine
progressively as the digestive contents move distally. As monophosphate, and may eventually degrade to uric
9
the rates of luminal carbohydrate digestion decrease, the acid. Uric acid is less soluble in plasma than inosine
generation of absorbable monosaccharide units also occurs monophosphate, has limited capacity for competitive
more slowly, resulting in less pronounced fluctuations renal secretion, and may form painful gouty lesions due
in plasma glucose and insulin concentrations following to inflammatory uric acid crystallization in tissues over
carbohydrate ingestion and digestion. As glycemic time when plasma concentrations exceed solubility levels. 17
excursions are attenuated, plasma insulin requirements The purpose of the present investigation was to determine
may plateau, typically at a lower level, as less insulin is the effects of partial luminal α-glucosidase inhibition
needed to facilitate immediate peripheral monosaccharide through the inclusion of MIG as a controlled dietary
uptake, oxidation, and disposal. The extended nature of admixture on plasma glycemic and lipid profiles. These
9,10
the fructose-induced insulinogenic response may trigger studies were conducted using an animal model where
a shift in insulin-stimulated secondary actions, including early-onset obesity, hyperinsulinemia, insulin resistance,
lipogenesis, glycogenesis, and modulation of plasma and T2DM develop in the obese phenotype due to the
insulin concentrations during the late post-prandial autosomal recessive inheritance of the -cp trait, with an
period. Thus, the insulin-lowering effect of α-glucosidase age of onset during early adolescence. 16,18-20 Due to this
activity, whether as a monotherapy or combined therapy, genetic predisposition, T2DM develops reproducibly in
may be enhanced in the presence of inhibitors of the obese offspring of both genders, independent of high-
luminal starch digestion. 9,11-15 In addition, because the fat diets or other dietary extremes. Furthermore, once
physiological half-life of insulin receptor activity typically expressed, the pathophysiologic stigmata of obesity and
extends considerably longer than that of starch digestion T2DM persist. 16-19 As noted, the epigenetic expression of
and subsequent monosaccharide uptake and oxidation, obesity and the subsequent progression to T2DM occur

Volume 4 Issue 2 (2025) 60 doi: 10.36922/gtm.6501