Japanese Journal of Medical Research
Open AccessImpact of Luminal Regulation of Hepatic Enzymes of Energy Metabolism in the Obese and Obese-Diabetic (T2DM) Corpulent Rat
Authors: Orien L Tulp, Syed AA Rizvi.
Abstract
The global prevalence of obesity+T2DM is approaching endemic proportions throughout much of Industrialized society, creating a challenge to health care resources, with no easy resolution on the horizon. This study aims to determine the effect of delayed carbohydrate (sucrose) digestion in type 2 diabetes mellites on the activity of glycemic and lipogenic enzyme parameters that directly or indirectly impact on carbohydrate and lipid metabolism and energy deposition. Groups (n=6-8/group, mean BW 264 ± 5g vs 263 ± 4g) of young adult male obese T2DM (diabetic) SHR/Ntul//-cp rats were fed a nutritionally complete USDA-formulated diet containing 54% sucrose (Control, CON) or the same diet with 150 mg of the luminal α-glucosidase inhibitor miglitol (MIG) for up to 8 weeks. Standardized analytical procedures established in our laboratory were utilized to quantify the findings. All animals demonstrated profound (4+) glycosuria by 8-10 weeks of age to confirm T2DM. Body Weight Gain (BWG), relative adiposity and glycosuria were elevated in CON animals. Measures of Oral Glucose Tolerance (OGT, 2.50 g glucose/kg BW, via gavage), AUC for glucose and insulin response to OGT and glycated hemoglobin (HbA1c) were elevated in controls and decreased by ~20% after MIG treatment. Hepatic Glucokinase (GK), and lipogenic NADPH-generating enzymes malic enzyme (ME) and glucose-6-phophate dehydrogenase (G6PD) were elevated in the CON and all decreased following MIG treatment. MIG was without effect on percent adiposity in lean rats of both strains or in the obese, non-diabetic LA/Ntul//-cp rats, but adiposity was decreased by ~10% in the obese-T2DM diabetic rats, consistent with the impact on lipogenic enzymes in T2DM. In conclusion, these observations indicate that luminal modulation of carbohydrate digestion can be an effective, cost-effective clinical strategy to improve the magnitude of the elevated glycemic and lipogenic enzymes and their subsequent impact on developing adiposity in the T2DM-prone obese+SHR/Ntul//-cp genetic rat strain, and may be an effective adjunct in clinical management of obesity, hyperlipidemia and T2DM as it occurs in man and animals.
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