RESUMEN
d-allulose is a rare sugar that has been reported to possess anti-hyperglycemic effects. In the present study, we hypothesized that d-allulose is effective in attenuating the progression of diabetic nephropathy in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of type 2 diabetes mellitus. Drinking water with or without 3% d-allulose was administered to OLETF rats for 13 weeks. Long-Evans Tokushima Otsuka rats that received drinking water without d-allulose were used as non-diabetic control rats. d-allulose significantly attenuated the increase in blood glucose levels and progressive mesangial expansion in the glomerulus, which is regarded as a characteristic of diabetic nephropathy, in OLETF rats. d-allulose also attenuated the significant increases in renal IL-6 and tumor necrosis factor-α mRNA levels in OLETF rats, which is a proinflammatory parameter. Additionally, we showed that d-allulose suppresses mesangial matrix expansion, but its correlation with suppressing renal inflammation in OLETF rats should be investigated further. Collectively, our results support the hypothesis that d-allulose can prevent diabetic nephropathy in rats.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/tratamiento farmacológico , Progresión de la Enfermedad , Fructosa/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Glucemia/metabolismo , Peso Corporal , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/orina , Conducta de Ingestión de Líquido , Ayuno/sangre , Ayuno/orina , Conducta Alimentaria , Fructosa/farmacología , Mediadores de Inflamación/metabolismo , Insulina/sangre , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Tamaño de los Órganos , Sustancias Protectoras/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Endogámicas OLETFRESUMEN
The rare sugar d-allulose is a C-3 epimer of d-fructose and is known to have several health benefits such as anti-obesity and anti-diabetic effects through the alteration of enzymatic and genetic expressions in each organ. Most of the ingested d-allulose is absorbed in the small intestine and then rapidly excreted in the urine. As d-allulose was reported to be present in the liver before it is excreted, d-allulose may modulate some hepatic metabolites including glucose and lipid metabolism. Therefore, we investigated the hepatic metabolomics profile in rats after feeding d-allulose to study the overall alteration of hepatic metabolism. Wistar rats were fed an AIN-93G diet with/without 3% d-allulose for 4 weeks. Their liver samples were then collected and subjected to metabolomics analysis using CE-TOFMS and LC-TOFMS. The results showed that d-allulose induced significant increases in 42 metabolites and significant decreases in 21 metabolites. In particular, we found at the substance levels that d-allulose regulated metabolites involved in the metabolic pathways of fatty acid ß-oxidation, cholesterol, and bile acid. In addition, this study newly showed the possibility that d-allulose alters glucuronic acid/xylulose pathways. In the future, we need more detailed research on the metabolomics profile of other organs related to these pathways for a comprehensive understanding of d-allulose functions.