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. 2013 Jul 9;14(7):14214-24.
doi: 10.3390/ijms140714214.

Molecular weight dependent glucose lowering effect of low molecular weight Chitosan Oligosaccharide (GO2KA1) on postprandial blood glucose level in SD rats model

Sung-Hoon Jo  1 , Kyoung-Soo Ha, Kyoung-Sik Moon, Jong-Gwan Kim, Chen-Gum Oh, Young-Cheul Kim, Emmanouil Apostolidis, Young-In Kwon
Affiliations

Molecular weight dependent glucose lowering effect of low molecular weight Chitosan Oligosaccharide (GO2KA1) on postprandial blood glucose level in SD rats model

Sung-Hoon Jo et al. Int J Mol Sci. .

Abstract

This research investigated the effect of enzymatically digested low molecular weight (MW) chitosan oligosaccharide on type 2 diabetes prevention. Three different chitosan oligosaccharide samples with varying MW were evaluated in vitro for inhibition of rat small intestinal α-glucosidase and porcine pancreatic α-amylase (GO2KA1; <1000 Da, GO2KA2; 1000-10,000 Da, GO2KA3; MW > 10,000 Da). The in vitro results showed that all tested samples had similar rat α-glucosidase inhibitory and porcine α-amylase inhibitory activity. Based on these observations, we decided to further investigate the effect of all three samples at a dose of 0.1 g/kg, on reducing postprandial blood glucose levels in Sprague-Dawley (SD) rat model after sucrose loading test. In the animal trial, all tested samples had postprandial blood glucose reduction effect, when compared to control, however GO2KA1 supplementation had the strongest effect. The glucose peak (Cmax) for GO2KA1 and control was 152 mg/dL and 193 mg/dL, respectively. The area under the blood glucose-time curve (AUC) for GO2KA1 and control was 262 h mg/dL and 305 h mg/dL, respectively. Furthermore, the time of peak plasma concentration of blood glucose (Tmax) for GO2KA1 was significantly delayed (0.9 h) compared to control (0.5 h). These results suggest that GO2KA1 could have a beneficial effect for blood glucose management relevant to diabetes prevention in normal and pre-diabetic individuals. The suggested mechanism of action is via inhibition of the carbohydrate hydrolysis enzyme α-glucosidase and since GO2KA1 (MW < 1000 Da) had higher in vivo effect, we hypothesize that it is more readily absorbed and might exert further biological effect once it is absorbed in the blood stream, relevant to blood glucose management.

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Figures

Figure 1
Figure 1
Dose dependent changes in rat intestinal α-glucosidase inhibitory activity (% inhibition) of chitosan oligosaccharides classified by molecular weight (GO2KA1; MW < 1000 Da, GO2KA2; MW 1000–10,000 Da, GO2KA3; MW > 10,000 Da). The results represent the mean ± S.D. of values obtained from three measurements. Different corresponding letters indicate significant differences at p < 0.05 by Duncan’s test. A−C First letter is among different samples and a−c second one is among different concentrations within same samples.
Figure 2
Figure 2
Dose dependent changes in porcine pancreas α-amylase inhibitory activity (% inhibition) of chitosan oligosaccharides classified by molecular weight (GO2KA1; MW < 1000 Da, GO2KA2; MW 1000–10,000 Da, GO2KA3; MW > 10,000 Da). The results represent the mean ± S.D. of values obtained from three measurements. Different corresponding letters indicate significant differences at p < 0.05 by Duncan’s test. A−C First letter is among different samples and a−c second one is among different concentrations within same samples.
Figure 3
Figure 3
Effect of GO2KA1 on sucrose loading test. After fasting for 24 h, six-week-old, male SD rats were orally administered with sucrose solution (2.0 g/kg) with or without samples (GO2KA1; MW < 1000 Da, positive control; Acarbose). Each point represents mean ± S.D. (n = 5). A−C Different corresponding letters indicate significant differences (p < 0.05) at 0.5 h by Duncan’s test. a−c Different corresponding letters indicate significant differences (p < 0.05) at 1.0 h by Duncan’s test.
Figure 4
Figure 4
Effect of GO2KA2 on sucrose loading test. After fasting for 24 h, six-week-old, male SD rats were orally administered with sucrose solution (2.0 g/kg) with or without samples (GO2KA2; MW 1000–10,000 Da, positive control; Acarbose). Each point represents mean ± S.D. (n = 5). A−C Different corresponding letters indicate significant differences (p < 0.05) at 0.5 h by Duncan’s test. a−c Different corresponding letters indicate significant differences (p < 0.05) at 1.0 h by Duncan’s test.
Figure 5
Figure 5
Effect of GO2KA3 on sucrose loading test. After fasting for 24 h, six-week-old, male SD rats were orally administered with sucrose solution (2.0 g/kg) with or without samples (GO2KA3; MW > 10,000 Da, positive control; Acarbose). Each point represents mean ± S.D. (n = 5). A−C Different corresponding letters indicate significant differences (p < 0.05) at 0.5 h by Duncan’s test. a−c Different corresponding letters indicate significant differences (p < 0.05) at 1.0 h by Duncan’s test.
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