D-Xylose as a sugar complement regulates blood glucose levels by suppressing phosphoenolpyruvate carboxylase (PEPCK) in streptozotocin-nicotinamide-induced diabetic rats and by enhancing glucose uptake in vitro
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BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia andinsulin resistance. D-Xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in bloodglucose levels. The objective of this study was to investigate the anti-diabetic effects of D-xylose both in vitro and stretpozotocin(STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS: Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabeticrats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with D-xylose; and (iv) diabeticrats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with D-xylose. These groupswere maintained for two weeks. The effects of D-xylose on blood glucose levels were examined using oral glucose tolerancetest, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK)expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion bydifferentiated C2C12 muscle cells and INS-1 pancreatic β-cells were analyzed. RESULTS: In vivo, D-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reducedthe area under the glucose curve, and increased insulin levels compared to the diabetic controls. D-Xylose supplementationenhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of D-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptakeby C2C12 cells and insulin secretion by INS-1 cells were increased with D-xylose supplementation in a dose-dependent mannercompared to treatment with glucose alone. CONCLUSIONS: In this study, D-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regenerationof damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, D-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by β-cells. These mechanisticinsights will facilitate the development of highly effective strategy for T2D.
Abstract
BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia andinsulin resistance. D-Xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in bloodglucose levels. The objective of this study was to investigate the anti-diabetic effects of D-xylose both in vitro and stretpozotocin(STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS: Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabeticrats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with D-xylose; and (iv) diabeticrats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with D-xylose. These groupswere maintained for two weeks. The effects of D-xylose on blood glucose levels were examined using oral glucose tolerancetest, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK)expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion bydifferentiated C2C12 muscle cells and INS-1 pancreatic β-cells were analyzed. RESULTS: In vivo, D-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reducedthe area under the glucose curve, and increased insulin levels compared to the diabetic controls. D-Xylose supplementationenhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of D-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptakeby C2C12 cells and insulin secretion by INS-1 cells were increased with D-xylose supplementation in a dose-dependent mannercompared to treatment with glucose alone. CONCLUSIONS: In this study, D-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regenerationof damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, D-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by β-cells. These mechanisticinsights will facilitate the development of highly effective strategy for T2D.
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