title: Effect of long-term supplementation of low molecular weight chitosan oligosaccharide (GO2KA1) on fasting blood glucose and HbA1c in db/db mice model and elucidation of mechanism of action.
abstract: BACKGROUND
  Type 2 diabetes is a serious problem for developed countries. Prevention of prediabetes progression to type 2 diabetes with the use of natural products appears to a cost-effective solution. Previously we showed that enzymatically digested low molecular weight chitosan-oligosaccharide with molecular weight (MW) below 1,000 Da (GO2KA1) has potential for hyperglycemia management.
  
  
  METHODS
  In this study we evaluated the effect of long-term supplementation of GO2KA1 on hyperglycemia using a db/db mice model. Additionally, we evaluated the effect of GO2KA1 on sucrase and glucoamylase activities and expression, using the same db/db mice model.
  
  
  RESULTS
  After 42 days we observed that GO2KA1 supplementation reduced both the blood glucose level and HbA1c in a similar manner with a known anti-diabetic drug, acarbose. When the sucrase and glucoamylase activities of GO2KA1 and control mice were evaluated using enzymatic assay, we observed that GO2KA1 significantly inhibited sucrase in all 3 parts of the intestine, while glucoamylase activity was significantly reduced only in the middle and lower part. When the sucrase-isomaltase (SI) complex expression on mRNA level was evaluated, we observed that GO2KA1 had minimal inhibitory effect on the upper part, more pronounced inhibitory effect on the middle part, while the highest inhibition was observed on the lower part. Our findings suggest that long-term GO2KA1 supplementation in db/db mice results to significant blood glucose and HbA1c reduction, to levels similar with those of acarbose. Furthermore, our findings confirm previous in vitro observations that GO2KA1 has inhibitory effect on carbohydrate hydrolysis enzymes, namely sucrase, maltase and SI complex.
  
  
  CONCLUSIONS
  Results from this study provide a strong rationale for the use of GO2KA1 for type 2 diabetes prevention, via inhibition of carbohydrate hydrolysis enzymes. Based on the findings of this animal trial, clinical trials will be designed and pursued.
authors: Jong-Gwan
authors: JG
authors: Kim
authors: Sung-Hoon
authors: SH
authors: Jo
authors: Kyoung-Soo
authors: KS
authors: Ha
authors: Sung-Chul
authors: SC
authors: Kim
authors: Young-Cheul
authors: YC
authors: Kim
authors: Emmanouil
authors: E
authors: Apostolidis
authors: Department of Food and Nutrition, Hannam University, Daejeon 305-811, Korea. youngk@hnu.kr.
authors: Young-In
authors: YI
authors: Kwon
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000517:prevention & control; D004435:Eating / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009844:Oligosaccharides / Q000494:pharmacology*; D011236:Prediabetic State / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D048271:Chitosan; D006442:Glycated Hemoglobin; D006026:Glycoside Hydrolases; D009844:Oligosaccharides