Aim To evaluate the inhibitory effect of chitosan-cysteine conjugate onenzymatic degradation and hypogly-cemic enhancement effect of insulin. Methods Chitosan-cysteineconjugate was synthesized. The protective effect o...Aim To evaluate the inhibitory effect of chitosan-cysteine conjugate onenzymatic degradation and hypogly-cemic enhancement effect of insulin. Methods Chitosan-cysteineconjugate was synthesized. The protective effect of the conjugate against degradation of insulin byα-chymotrypsin and trypsin was evaluated in vitro. Insulin enteric- microspheres were prepared byusing O_1 /Q_2 emulsion solvent evaporation method. The hypoglycemic enhancement effect of theconjugate was studied by oral administration of insulin solution or enteric-microspheres to rats.Results The thiol group content of the synthesized conjugate was about 200 μmol·g^(-1) polymer,which showed a strong protective effect on insulin from enzymatic degradation in vitro. Almost allthe insulin incubated in a-chymotrypsin solution or trypsin solution without chitosan-cysteineconjugate was degraded entirely within 1 h and 5 h respectively, whereas above 75% of insulinremained in the same content of the enzymatic solution containing 4 mg·mL^(-1) conjugate. The drugloading of insulin enteric-microspheres was about 7% . In vivo experiment, chitosan-cysteineconjugate (85 μg·kg^(-1)) prolonged the hypoglycemic time of insulin solution orenteric-microspheres when administered simultaneously with the absorption enhancer SNAC. ConclusionChitosan-cysteine conjugate has a marked inhibitory effect on the enzymatic degradation of insulinin vitro, and it displays a significant hypoglycemic enhancement effect on insulin oral formulationin vivo.展开更多
OBJECTIVE:To investigate the effects of cinnamaldehyde(CA),an active and major compound in cinnamon,on glucose metabolism and insulin resistance in C57BLKS/J db/db mice.METHODS:Sixteen male C57BLKS db/db mice were ran...OBJECTIVE:To investigate the effects of cinnamaldehyde(CA),an active and major compound in cinnamon,on glucose metabolism and insulin resistance in C57BLKS/J db/db mice.METHODS:Sixteen male C57BLKS db/db mice were randomly divided into control and CA treatment groups.CA was given(20 mg.kg-1.day-1,p.o.) for 4 weeks.Pure water was given to control and db/+ mice.Subsequently,the levels of fasting blood glucose(FBG),fasting serum insulin,triglyeride,cholesterol,low-density lipoprotein-cholesterol(LDL-C),high-density lipoprotein-cholesterol(HDL-C),and free fatty acids(FFA),as well as the mRNA content of adiponectin and tumor necrosis factor(TNF)-α in adipose tissue,glucose transporter type 4(GLUT-4) in skeletal muscle,and protein expressions of Akt,phospho-Akt(Thr308),AMPKα,phospho-AMPKα(Thr172) in skeletal muscle were measured.RESULTS:1) CA decreased serum levels of FBG and insulin as well as body weight in db/db mice;2) CA increased serum HDL-C levels;3) CA significantly decreased the mRNA expression of TNF-α in adipose tissue and upregulated mRNA expression of GLUT-4 in skeletal muscle;4) protein expression of p-Akt was increased in CA-treated mice,but Akt,AMPKα and p-AMPKα showed no change.CONCLUSION:CA has antihyperglycemic and antihyperlipidemic actions in db/db mice and could be useful in the treatment of type-2 diabetes.展开更多
文摘Aim To evaluate the inhibitory effect of chitosan-cysteine conjugate onenzymatic degradation and hypogly-cemic enhancement effect of insulin. Methods Chitosan-cysteineconjugate was synthesized. The protective effect of the conjugate against degradation of insulin byα-chymotrypsin and trypsin was evaluated in vitro. Insulin enteric- microspheres were prepared byusing O_1 /Q_2 emulsion solvent evaporation method. The hypoglycemic enhancement effect of theconjugate was studied by oral administration of insulin solution or enteric-microspheres to rats.Results The thiol group content of the synthesized conjugate was about 200 μmol·g^(-1) polymer,which showed a strong protective effect on insulin from enzymatic degradation in vitro. Almost allthe insulin incubated in a-chymotrypsin solution or trypsin solution without chitosan-cysteineconjugate was degraded entirely within 1 h and 5 h respectively, whereas above 75% of insulinremained in the same content of the enzymatic solution containing 4 mg·mL^(-1) conjugate. The drugloading of insulin enteric-microspheres was about 7% . In vivo experiment, chitosan-cysteineconjugate (85 μg·kg^(-1)) prolonged the hypoglycemic time of insulin solution orenteric-microspheres when administered simultaneously with the absorption enhancer SNAC. ConclusionChitosan-cysteine conjugate has a marked inhibitory effect on the enzymatic degradation of insulinin vitro, and it displays a significant hypoglycemic enhancement effect on insulin oral formulationin vivo.
基金Supported by International Science and Technology Cooperation Project(grant number 2009DFA31520)Innovation Team Project of Beijing University of Chinese Medicine (2011-CXTD-19)Beijing Municipal Education Commission(2011)
文摘OBJECTIVE:To investigate the effects of cinnamaldehyde(CA),an active and major compound in cinnamon,on glucose metabolism and insulin resistance in C57BLKS/J db/db mice.METHODS:Sixteen male C57BLKS db/db mice were randomly divided into control and CA treatment groups.CA was given(20 mg.kg-1.day-1,p.o.) for 4 weeks.Pure water was given to control and db/+ mice.Subsequently,the levels of fasting blood glucose(FBG),fasting serum insulin,triglyeride,cholesterol,low-density lipoprotein-cholesterol(LDL-C),high-density lipoprotein-cholesterol(HDL-C),and free fatty acids(FFA),as well as the mRNA content of adiponectin and tumor necrosis factor(TNF)-α in adipose tissue,glucose transporter type 4(GLUT-4) in skeletal muscle,and protein expressions of Akt,phospho-Akt(Thr308),AMPKα,phospho-AMPKα(Thr172) in skeletal muscle were measured.RESULTS:1) CA decreased serum levels of FBG and insulin as well as body weight in db/db mice;2) CA increased serum HDL-C levels;3) CA significantly decreased the mRNA expression of TNF-α in adipose tissue and upregulated mRNA expression of GLUT-4 in skeletal muscle;4) protein expression of p-Akt was increased in CA-treated mice,but Akt,AMPKα and p-AMPKα showed no change.CONCLUSION:CA has antihyperglycemic and antihyperlipidemic actions in db/db mice and could be useful in the treatment of type-2 diabetes.
