Molecular Weight Dependent Glucose Lowering Effect of Low Molecular Weight Chitosan Oligosaccharide (GO2KA1) on Postprandial Blood Glucose Level in SD Rats Model

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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“…This is the first kind of study performed to determine the anti-diabetic activity and standardizing dose of chitosan and chitooligosaccharides (chitin-based derivatives) in treatment of diabetes. The results are satisfies the previous studies reported [14][15][16][17][18] .…”

Monoterpenes: Novel insights into their biological effects and roles on glucose uptake and lipid metabolism in 3T3-L1 adipocytes

“…Nonetheless, the main drawbacks of acarbose are gastrointestinal effects including abdominal distention, flatulence, meteorism and possibly diarrhea, due to abnormal fermentation of undigested carbohydrates by colonial bacteria as a result of over inhibition of a-amylase (Jo et al, 2013). A more effective strategy in the control of T2DM involves a moderate a-amylase inhibition with a stronger inhibition on a-glucosidase.…”

“…Inhibition of these enzymes delays overall carbohydrate digestion and glucose absorption rate consequently blunting the increase of postprandial plasma glucose level. Thus, carbohydrate-hydrolyzing enzyme inhibitors such as acarbose, miglitol and voglibose have been clinically used as oral anti-hyperglycemic agents in the effective control of T2DM (Jo et al, 2013;Sugihara et al, 2014).…”

Chitosan Modulates Inflammatory Responses in Rats Infected with Enterotoxigenic Escherichia coli

“…The chitosan particles bind with cholesterol and fatty acids to form clusters in the gastrointestinal tract, thereby reducing lipid absorption [20]. In addition to its effect on lipid absorption, chitosan has been described as reducing blood glucose levels and being capable of inhibiting the carbohydrate hydrolysing enzymes maltase, sucrose, and sucrose-isomaltase in the gut [21, 22]. …”