Nutr Res Pract.  2016 Feb;10(1):11-18. 10.4162/nrp.2016.10.1.11.

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

• Kim E
• Kim YS
• Kim KM
• Jung S
• Yoo SH
• Kim Y

• KMID: 2313895
• DOI: http://doi.org/10.4162/nrp.2016.10.1.11

Abstract

BACKGROUND/OBJECTIVES
Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia and insulin resistance. D-Xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in blood glucose 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) diabetic rats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with D-xylose; and (iv) diabetic rats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with D-xylose. These groups were maintained for two weeks. The effects of D-xylose on blood glucose levels were examined using oral glucose tolerance test, 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 by differentiated C2C12 muscle cells and INS-1 pancreatic beta-cells were analyzed.
RESULTS
In vivo, D-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. D-Xylose supplementation enhanced 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 uptake by C2C12 cells and insulin secretion by INS-1 cells were increased with D-xylose supplementation in a dose-dependent manner compared to treatment with glucose alone.
CONCLUSIONS
In this study, D-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regeneration of 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 beta-cells. These mechanistic insights will facilitate the development of highly effective strategy for T2D.

Keyword

D-xylose; sugar-complement; diabetes; PEPCK; glucose uptake

MeSH Terms

Animals
Blood Glucose*
Complement System Proteins*
Diet
Fasting
Gluconeogenesis
Glucose Tolerance Test
Glucose*
Hepatocytes
Hyperglycemia
Insulin
Insulin Resistance
Liver
Models, Animal
Muscle Cells
Pancreas
Phosphoenolpyruvate Carboxylase*
Phosphoenolpyruvate*
Rats*
Rats, Wistar
Regeneration
Sucrase
Sucrose
Xylose*
Blood Glucose
Complement System Proteins
Glucose
Insulin
Phosphoenolpyruvate
Phosphoenolpyruvate Carboxylase
Sucrase
Sucrose
Xylose

Figure

• 

  Fig. 1 Effects of D-xylose on body weight and glucose tolerance test (OGTT) levels. Male Wistar rats (n = 8-9/group) were injected with streptozotocin and nicotinamide to induce type 2 diabetes. Two groups of normal control and diabetes control received the 93G diet for two weeks. Other two groups of these rats received a diet containing 5% (Xylo 5) or 10% (Xylo 10) of the total sucrose content in the 93G diet was replaced with D-xylose for two weeks. The effect of D-xylose on (A) final body weight, (B) the OGTT, and (C) the OGTT area under the curve (AUC) are shown. The values shown are the mean ± SEM. Letters are used to indicate the values that significantly differ from each other (P < 0.05). DB, diabetes control.

• 

  Fig. 2 Effects of D-xylose on the fasting blood glucose and insulin secretion levels. (A) Fasting blood glucose level, and (B) insulin level are shown for the four experimental rat groups. The values shown are the mean ± SEM. Letters are used to indicate the values that significantly differ from each other (P < 0.05). DB, diabetes control; Xylo 5 or Xylo 10, rat groups that received diets where 5% or 10%, repectively, of the total sucrose content of the diets was replaced with D-xylose

• 

  Fig. 3 Effects of D-xylose on histopathological changes in the pancreas. Pancreatic histopathological features were observed for the four experimental rat group: (A) normal control, (B) DB control (C) Xylo 5, and (D) Xylo 10. Tissues were stained with H&E. Scale bar = 50 µm Magnification 400 ×. DB, diabetes control; Xylo 5 or Xylo 10, rat groups that received diets where 5% or 10%, repectively, of the total sucrose content of the diets was replaced with D-xylose

• 

  Fig. 4 Effects of D-xylose on histopathological changes in the liver, and changes in PEPCK expression in the liver. (A) Hepatic histopathological features were observed for the four experimental rat groups: (a) normal control, (b) DB control, (c) Xylo 5, and (d) Xylo 10. (B) Levels of PEPCK in the liver were assessed using Western blotting assays. Representative blots are shown (upper panel). Band intensities were quantified by densitometry (lower panel) and were analyzed using one-way ANOVA with Newman-Keuls post hoc test (P < 0.05, n = 10 mice per group). The values shown are the mean ± SEM. Letters are used to indicate the values that significantly differ from each other (P < 0.05). Tissues were stained with H&E. Scale bar = 50 µm Magnification 400 ×. DB, diabetes control; Xylo 5 or Xylo 10, rat groups that received diets where 5% or 10%, repectively, of the total sucrose content of the diets was replaced with D-xylose; PEPCK, phosphoenol- pyruvate caroxylase.

• 

  Fig. 5 Effects of D-xylose on 2-NBDG uptake by C2C12 cells and insulin secretion by INS-1 pancreatic β-cells. The effect of glucose (A) or D-xylose (B) on 2-NBDG uptake by C2C12 skeletal muscle cells was assayed. Cells were treated with 100 nM insulin, Xylo 5, or Xylo 10, and 2-NBDG uptake assays were performed (see Materials and Methods). The effect of glucose (C) or D-xylose (D) on insulin secretion by INS-pancreatic β-cells was analyzed. The values shown are the mean ± SEM. Letters are used to indicate the values that significantly differ from each other (P < 0.05). Ins, insulin (a positive control); Glu, glucose; Xylo 5 or Xylo 10, treatment with 5% or 10% of the total glucose content of media was replaced with D-xylose

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