Chitosan and chitosan oligosaccharide Progress diabetes

Of: Xiao-Hua Liu Li Shumei Xiafang Lian credit risk Management

[Keywords:] chitosan, chitosan oligosaccharide, diabetes, review

Diabetes mellitus (DM) is the absolute or relative lack of insulin the body caused by blood sugar, urine sugar increased as the main feature of the syndrome of chronic metabolic disorders, often accompanied by determined to brain blood vessels, kidney, eye and nerve and other complications. It is the second vicious cancer, cardiovascular and cerebrovascular disease after three serious threat to human health of the slow disease. According to a large number of clinical observations, commonly used hypoglycemic agents such as insulin, glibenclamide and so on, although a certain effect, but its obvious side effects, there is no one species can simultaneously control the effective treatment of complications of DM drugs for clinical medical treatment has brought great challenges DM (1). chitosan (Chitosan) is the product of deacetylation of chitin, is the nature of production second only to Trona in the second largest cellulose polysaccharides, immune regulation, anti-cancer, lowering blood sugar, cholesterol, and so many features and good biological adhesion, biocompatibility, and has extensive applications in medicine (2). oligosaccharide (Chitooligosaccharides, COS) is a degradation product of chitosan, soluble in water, conducive to human intestinal digestion and absorption, higher than the biological activity of chitosan and the more physiological functions, is a safe and reliable natural polysaccharide (3). COS home and abroad in recent years for the treatment of DM increasing as the treatment of DM and its complications to open a new direction.

1 The Influence of chitosan on the role of DM

1.1 The effect of chitosan on blood glucose in DM

As we all know, rationally and effectively control the blood sugar level is the key to DM treatment. MING AND, etc. (4) studies show that chitosan lobster DM alloxan hypoglycemic mice and enhanced the role of glucose tolerance, while the normal mice no significant effect on blood sugar levels, research has also replicated with SD rats alloxan DM, after chitosan treatment, blood glucose levels decreased significantly increased serum insulin levels, which may reduce free radical damage and its affect plasma endothelin Nitric Oxide generation and to promote the recovery of -cell damage related to (5). Kondo and other studies suggest that chitosan can act on insulin receptors, increased sensitivity to inhibition effect of hyperglycemia (6), also Data show that chitosan has good hypoglycemic effect, and the toxic side effects can be avoided oral hypoglycemic agents of chemical effects of low blood sugar (7).

1.2 The effect of chitosan on lipid DM

Studies have shown that chitosan is a positively charged organic polymers, can absorb negative foods with fat, block fat break down and absorb cholesterol and bile acids, so fat is not absorbed in the intestines from the body, thus reduced lipid content (8), Yang Ming Duo, etc. (9) in vitro digestion simulation studies show that chitosan ratio was 1:8 with the bile acid, it can better complexation of bile acids, interfere with the body's absorption of fat. with streptozotocin (STZ)-induced rat model of type DM increased blood cholesterol, absorption of bile acid by chitosan, the cholesterol can not be enzymatic cholesterol, reduce blood cholesterol levels play a role (10), WANG Shu-ling et al (11) further pointed out that led to the blood glucose lowering serum cholesterol and triglyceride levels decreased significantly. chitosan on blood lipids of DM there are other mechanisms. For example, a study (12) that chitosan reduced fat may be related to the role of the amino group content on the structure, through the bridging effect of amino electrostatic adsorption of free fatty acids, the lipid drop type DM.

1.3 The use of chitosan on the impact of insulin-DM

With the global rise in the prevalence of DM, the use of a corresponding increase in the number of insulin, because of its digestive protease susceptible to degradation oral invalid to injection, which caused inconvenience to patients and pain. Some studies that, due to bioadhesive chitosan, the positive charge and so to promote the absorption of insulin has a good effect on improving the bioavailability of insulin plays an important role (13). Some studies (14) insulin using chitosan coated lipid body, obtained under the optimum conditions for preparation of products by rats and mice after oral administration, blood glucose levels dropped to the lowest pre-test were 39.13% and 16.94%. Huang Hui et al (15) further pointed out that chitosan sugar insulin microspheres for oral preparation streptozotocin induced DM rats have a certain mechanism of hypoglycemic effects of chitosan may be due to alkaline, the insulin microspheres encapsulated and good targeting, and gradually release insulin and play a role in lowering blood sugar, and 3 h after administration of rat intestinal epithelial cells and chitosan microspheres have a strong interaction between the (16). islet transplantation is more effective treatment of DM, one of the means, it can be alleviate the serious shortage of donor islet contradiction. F Wenhui et al (17) with a successful model STZ mice, we found that chitosan alginate microencapsulated Tong Polyethylene glycol correctable islet xenotransplantation in mice DM, and to overcome other shortcomings of poor biocompatibility, and excellent biocompatibility, chitosan microcapsules that can be regulated degradation characteristics in the field of islet transplantation has broad application prospects.

1.4 chitosan on the role of gene therapy for DM

In addition to the treatment of type DM exogenous insulin injections, but neither can other practical way to achieve long-term remission patients, and no effective methods to prevent the occurrence of the disease. Chitosan for gene therapy of type DM has been some encouraging exploration. Foreign Studies (18) the use of chitosan in vivo or in vitro plasmid DNA into cells or body tissue, that its biggest advantage is safety, non-toxic, and has good tissue compatibility, the study also show that the interaction between chitosan and DNA through electrostatic, and only when they enter the cells until after the dissociation, and it also effectively embedded DNA, to prevent degradation of DNA by DNA enzymes to improve the transfection efficiency (19). domestic research (20,21) reported that in vitro transfection using chitosan mouse fibroblast cells was transfected with recombinant plasmid about 10% of the cells the expression of insulin and insulin expression vector that DM cells significantly decreased blood glucose, body weight gradually recovered. All this shows that the human insulin gene could transfect non-islet cells, and the expression of target genes to decrease blood sugar levels, therefore, chitosan is a promising gene carrier of insulin.

2 COS on the role of DM

Japan already has the patent in 2002 (22) reported that low molecular weight chitosan (ie, COS and the role of salt with anti-diabetes, can be used to treat DM. Some studies (23) showed that in mice with high doses of DM can COS significantly lower blood sugar, high doses to pancreatic cells increased, and its hypoglycemic mechanism may promote the proliferation of pancreatic cells. Hayashi et al (24) studies have indicated that 0.8% of Chitooligosaccharides and obese mice to STZ DM DM-type mice showed significant improvement of postprandial blood glucose in serum, a study further pointed out that chitin and its derivatives (including the COS in the role of gastric acid can be dissolved and colloidal presented to extend the food the stomach emptying time, and delay and reduce the intestinal absorption of sugar, together in the small intestine @ glucosidase inhibitory effect, which can reduce postprandial hyperglycemia, reducing the stimulation of insulin secretion and cell burden, to maintain its normal function (25, .) reported otherwise, crustaceans oligosaccharides can induce non-obese DM in vitro proliferation of mouse pancreatic islet cells leaving increased insulin secretion (26).

Some of the domestic (27 ~ 30) reported that DM induced by STZ rats fed low molecular weight chitosan, the results show that, COS can significantly reduce blood glucose, blood lipid levels, blood insulin levels to rise, and to fight against weight reduce, alleviate symptoms of DM, also pointed out that glucose may islet cells by promoting repair, improve insulin secretion, increased peripheral tissue sensitivity to insulin and other mechanisms to lower blood sugar, and further pointed out that the COS can regulate a large DM The main mechanism of mice with COS adsorption of lipid fat, bile acids, cholesterol in the liver to promote conversion and so on. foreign Lee et al (31) studies have shown that given STZ induced DM rats with non-insulin dependent diabetes fasting blood glucose 0.3% lower after oligosaccharide 19%, glucose tolerance gradually increased and triglyceride decreased by 49%, cholesterol dropped by 10%, a significant increase in insulin secretion, which may improve -cell function and insulin secretion to normalize the results.

3 Prospects

COS is the chitosan and its degradation products in developing countries in the world in recent years, the fourth generation of functional health products, in the fight against DM and its complications has demonstrated a broad application prospects. Of course, they also applied to prevention and treatment of DM many aspects worthy of further exploration. For example, in addition to the structure of amino, there are hydroxyl groups, to introduce some functional groups to increase their biological activity, expand the application areas, preparation of insulin using chitosan microspheres as a carrier to achieve the oral application of insulin still need to improve its bioavailability, improved production process, and microspheres of biodegradable chitosan in vivo half-life and so further research, -type DM, although gene therapy has made some progress, but it is just the beginning stage, COS Research on the impact of DM are not many studies in this area should be strengthened, and, chitosan and COS study of DM and its complications remain in most animal experimental stage, have not yet entered clinical application.

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1 Pan Changyu. Diabetes (M). 14th Edition. Beijing: People Health Press, 2007:610.

2 Chiang getting bigger. Chitosan (M). Beijing: China Environmental Science Press, 2001:210 8.

3 Tsai GJ, Wu ZY, Su WH.Antibacterial activity of a chitooligosaccharide mixture prepared by cellulase digestion of shrimp chitosan and its applieation to milk preservation (J). J Food Prot, 2002, 63 (6): 747 52.

4 MING Wang Yana, were Aiping. Lobster chitosan blood sugar after the intervention and changes in glucose tolerance (J). Chinese Journal of Clinical Rehabilitation, 2006,10 (31): 679.

5 Wu Yong, Jing-Ping Ouyang, Tu Shu-zhen, et al. Astragalus polysaccharides on the role of microangiopathy in diabetic rats and the mechanism (J). Hubei Medical College, 2001,3 (3): 16.

6 Kondo Y, Nakatani A, Hayashi K, et al.Low molecular weight chitosan prevents the progression of low dose streptozotocin induced slowly progressive diabetes mellitus in mice (J). Boil Pharm Bul1, 2000,23 (12:1458 64.

7 Derek E, Woodgate MSC, Julie A, et al.Effects of a stimulant free dietary supplement on body weight and fat loss in obese adults: a six week exploratory study (J). Curr Therap Res, 2003,64 (4): 24862.

8 De Campos Grifoni S, Bendhack LM.Functional study of the (Ca2 +), signling pathway in aortas of L NAME hypertensive rat (J). Pharmacolgy, 2004,70 (3): 160 8.

9 Yang Ming Duo, Liu Haoyu, Wang Wo, et al. Chitosan role of fat suppression (J). Nutrition, 2002,24 (1): 53 7.

10 Qi XH.Therapeutic effect and mechanisms of ehitosan compound on rats of experimental fatty liver (J). Pharmacology, 2004,2 (5): 285 7.

11 WANG Shu-ling TRAUMA AND. Chitosan on blood glucose in type 2 diabetic rats, blood lipids, cholesterol content (J). Modern Journal of Integrated Traditional and Western, 2007,16 (6): 7379.

12 Tai TS, Sheu WH, Lee WJ, et al.Effect on chitosan on plasma lipoprotein concentrations in type 2 diabetic subjects with hypercholesterolemia (J). Diabetes Care, 2000, 23 (11): 1703 4.

13 Wu ZH, Ping QN, Wei Y, et al.Hypoglycemic efficacy of chitosan coated insulin liposomes after oral administration in mice (J). Acta Pharmacol Sin, 2004,25 (7): 966 72.

14 Wu Hung, Ping of its energy, Wei Yi, et al. Chitosan coated insulin liposomes formulation and process optimization (J). Chinese Journal of Pharmaceuticals, 2003,34 (2): 76 80.

15 Huang Hui, Tian Haoming, Li Xiongwei, et al. Chitosan microspheres of insulin in the blood glucose in diabetic rats Effect of (J). Journal of Biomedical Engineering, 2001,18 (3): 425 8.

16 Ma Z, Lim TM, Lim LY.Pharmacological activity of peroral chitosan insulin Nanoparticles in diabetic rats (J). Int J Pharm, 2005,293 (1 2): 271 80.

17th Floor, Wen Hui, Qin Xinyu, Wu Zhaoguang. Chitosan and polyethylene glycol alginate microencapsulated islet xenotransplantation in mice treated diabetes (J). Journal of Experimental Surgery, 2001,18 (6): 548 50.

18 Koping Hoggard M, Tubulekas I, Guan H, et al.Chitosan as a nonviral gene delivery system.Structure property relationships and characteristics compared with polyethylenimine in vitro and after lung administration in vivo (J). Gene Therapy, 2001,8 (14 ): 1108 21.

19 Mao HQ, Roy K. Chitosan DNA hanoparticles as gene carriers: synthesis, characterization and transfection efficiency (J). J Control Realse, 2001,70 (3): 399 421.

20 Journal of Asian and African, Guo Qingyun, Xu Yan, et al. Chitosan-mediated insulin gene expression in diabetic rats in vivo studies (J). New Medicine, 2005,15 (2): 42 4.

21 Niu Li, Xu Yan-cheng, Guo Min. Human insulin gene expression in diabetic rats (J). Public Health and Preventive Medicine, 2005,16 (3): 17 9.

22 Ito Mikio, Hamaishi Kanoko, Hayashi Koji, et al.Antidiabetic effect promoter for promoting antidiabetie effect of insulin formulation and for treating hyperglycemia, contains oral composition containing low molecular chitosan and / or their salts as active ingredient (P). JP, 2004067575 A, 2002.8.

23 Yanchun Ling, PROCEEDINGS, Liu Bing. Low molecular weight water-soluble chitosan on blood glucose of diabetic mice (J). Qingdao University Medical College, 2006,42 (4): 352 3.

24 Hayashi K, Ito M. Antidiabetic action of low molecular weight chitosan in genetically obese diabetic KK Ay mice (J). Boil Pharm Bull, 2002; 25 (2): 188 92.

25 Fang, Cao Zhaohui, Li Bangliang. Chitin and its derivatives on the role of diabetes mellitus (J). Pancreatic Diseases, 2005,5 (4): 255 6.

26 Qiao Xinhui, Song Lan, Li Bangliang, et al. Chitooligosaccharides non-obese diabetic mouse islet cells and insulin secretion of (J). Journal of clinical research, 2003,20 (4): 259 60.

27 EMERGENCY, Wu Yong, Li Meiping, et al. Low molecular weight chitosan on experimental regulation of blood glucose in diabetic rats (J). Hubei Medical College, 2005,7 (1): 18 20.

28 Liu B, Liu WS, Han BQ, et al.Antidiabetic effects of Chitooligosaccharides on pancreatic islet cells in streptozotocin induced diabetic rats (J). World J Gastroenterol, 2007,13 (5): 725 31.

29 EMERGENCY, Wu Yong, Peng Yuan, et al. Low molecular weight chitosan on blood glucose, blood lipid content (J). Chinese Journal of Gerontology, 2005,25 (5): 5413.

30 Liu Bing, PROCEEDINGS, Han Baoqin, et al. Chitosan oligosaccharide and its derivatives on the regulation of blood lipids in experimental diabetic rats and the antioxidant (J). Shandong University (Natural Science), 2006,41 (4): 15863 .

31 Lee HW, Park YS, Choi JW, et al.Antidiabetic effects of chitosan oligosaccharides in neonatal streptozotocin induced nonisulin dependent diabetes mellitus in rats (J). Boil Pharm Bull, 2003,26 (18): 1100 3.

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