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Global Translational Medicine Glucosidase and metabolic profiles

ingestive absorption or systemic distribution, the risk metabolic sequelae, with no apparent rebound effects,
of hepatic or other organ toxicity is minimal. MIG, the metabolic complications, or adverse side effects. Indeed,
focus of this study, is a complex oligosaccharide that acts during necropsy, no pathophysiological aberrations were
as a competitive, reversible inhibitor of membrane-bound observed in the MIG-treated animals. An earlier study
intestinal α-glucoside hydrolase activity. 9,25-29 Luminal also observed a similar pattern of decreased food intake
modulators of starch digestion, including acarbose and when the glucosidase inhibitor acarbose was fed as an
MIG, have been found to be useful agents in treating mild admixture to lean and obese non-diabetic rats, resulting
to moderate T2DM. 9,21-25 In a previous animal study lasting in comparable improvements in glycemic responses,
less than 8 weeks with the MIG analog acarbose, HbA1c, adiposity, and plasma lipid parameters. The evidence
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and glycemic responses demonstrated improvement from the present study suggests that the dietary regimen
toward normalization over time. The results of this study linked improvements in glucose AUC, HbA1c, lipid
9
are also consistent with previous clinical findings in the profiles, and weight gain, consistent with improvements
Wistar Fatty Rat and further confirm that an 8-week trial in insulin action in peripheral tissues, including skeletal
of feeding a highly palatable, high carbohydrate, sucrose- muscle and adipose tissue, which are major sources of
laden diet to obese adult Wistar Fatty Rats with well- peripheral insulin resistance in obesity and T2DM. 41,42
established T2DM is sufficient to induce improvements
in glycemic parameters, including reductions in excess Although not studied in the present investigation,
adiposity and weight gain. The metabolic similarity in the contributions of inflammatory cytokines, including
the development of insulin resistance between the obese tumor necrosis factor-alpha, interleukin-6, C-reactive
phenotypes of the Wistar fatty rat, SHR/Ntul//-cp rats, protein, and nuclear factor kappa B, were not determined.
and other similar models contributes to the development Numerous studies in rodents and cell cultures have linked
of the obese and T2DM phenotype in these animal elevated plasma lipids and fatty acids to the generation
models. All these models demonstrated significant of inflammatory markers, which are associated with
improvements in glycemic parameters when treated with endothelial dysfunction, a common issue in T2DM and
the glucosidase inhibitor regimen, including a reduction its comorbidities. 43-47 While the molecular mechanisms
in chronic hyperphagia commonly associated with the of these cytokines remain unclear, insulin resistance is
obese phenotype. 9,10,38 As reported by Boque et al., when commonly observed when levels of monocyte-derived
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lean male Wistar rats were fed a similar high-carbohydrate inflammatory cytokines are elevated, contributing to
diet, an increase in fasting triglyceride concentrations was the risk for T2DM. Given that T2DM is one of the most
observed. In the present study, the MIG treatment was common metabolic disorders worldwide, cost-effective
associated with improvements in glycemic parameters, agents such as MIG could decrease plasma lipid levels,
plasma triglycerides, total cholesterol, LDL-cholesterol, improve glycemic status, and reduce the trend toward
and HDL cholesterol fractions, as well as a reduction in greater adiposity. These pharmacological benefits could
sucrose-linked weight gain, a decrease in the glucose AUC, make MIG a valuable treatment, similar to the well-
and a reduction in HbA1c levels. established anti-inflammatory and cholesterol-lowering
effects of statins on cardiovascular diseases, which are now
Because only animals of the obese-T2DM phenotype widely prescribed with minimal side effects. Future studies
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were included in this study, it was not possible to determine of α-glucosidase inhibitors could determine whether such
whether the final weight and metabolic profiles would a regimen could prevent or delay the onset of T2DM and
have been similar to those of their lean littermates if they its sequelae in both humans and animals, as prevention is
had been fed similar diets over the 8-week duration of generally preferred over long-term management.
the observations. However, as the obese rats were already
significantly heavier than their lean littermates at the In summary, improvements in plasma lipid and
beginning of the study (average lean = 235 ± 6 g vs. obese glycemic profiles in the obese and T2DM phenotype
= 264 ± 19 g at 8 weeks of age; p<0.05), and the T2DM of this and other strains following luminal glucosidase
characteristics were well-established, it is likely that longer inhibition have been clearly established despite only
treatment would have been necessary for full resolution. modest improvements in insulin resistance as assessed
This is especially relevant as hyperinsulinemia and by HOMA analysis. Without treatment, increases in
atheroma development typically begins soon after weaning biochemical markers for free radicals are consistent with
in this and other similar strains. 8-26,38,39 In the present study, atherogenic lipid profiles, including elevations in serum
the decreases in net energy intake and weight gain averaged triglycerides, cholesterol, and LDL-cholesterol fractions,
15% following the MIG feeding regimen, indicating a which are indicative of senescent, atherogenic alterations
favorable correlation between the dietary impact and in the vascular intima. Although the glycemic and lipid
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Volume 4 Issue 2 (2025) 66 doi: 10.36922/gtm.6501