Type 2 diabetes(T2D)presents a significant health challenge,underscoring the need for functional foods and nutraceutical hypoglycemic bioactive peptides for its prevention.This study investigates the potential of prot...Type 2 diabetes(T2D)presents a significant health challenge,underscoring the need for functional foods and nutraceutical hypoglycemic bioactive peptides for its prevention.This study investigates the potential of proteolytic hydrolysate from artificially cultivated Chinese giant salamander(CGS)meat,a rich protein source,as a preventive strategy for T2D.We produced a CGS meat hydrolysate(CGSh)and demonstrated its ability to inhibit the T2D drug target dipeptidyl peptidaseⅣ(DPP-Ⅳ)through in vitro assays.We identified 5 peptides(WRPPDH,WAPPSKD,IPDSPF,IPEMIF,and VPIAVPT)with high DPP-Ⅳinhibitory activity in CGSh,suggesting its potential antidiabetic effects.In vivo experiments showed that CGSh effectively reduced insulin resistance in mice induced with a high-fat diet,as evidenced by a slower increase in blood glucose levels and a decreased HOMA-IR index.16S rRNA sequencing analysis revealed that CGSh improved gut microbial homeostasis,promoting beneficial microorganisms and reducing harmful bacteria.Metabolomic analyses identified an increase in valeric acid levels and highlighted nine potential biomarker metabolites.By inhibiting metabolic pathways such as AGE-RAGE,CGSh might also prevent diabetic complications and reduce inflammation.These findings suggest that CGSh has a promising hypoglycemic effect,making it a potential functional food ingredient for T2D prevention and treatment.展开更多
This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma co...This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma concentration-time curve(AUC)of cilastatin were significantly increased,while renal clearance and cumulative urinary excretion of cilastatin were decreased.At the same time,imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1(hOAT1)-HEK293 and human OAT3(hOAT3)-HEK293 cells.Probenecid,p-aminohippurate,and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1-and hOAT3-HEK 293 cells,respectively.The uptakes of imipenem and cilastatin in hOAT1-and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells.Moreover,the K m values of cilastatin were increased in the presence of imipenem with unchanged V max,indicating that imipenem inhibited the uptake of cilastatin in a competitive manner.When imipenem and cilastatin were co-administered,the level of imipenem was higher compared with imipenem alone both in vivo and in vitro.But,cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1(DPEP1)was silenced by RNAi technology in hOAT1-and hOAT3-HEK 293 cells.In conclusion,imipenem and cilastatin are the substrates of OAT1 and OAT3.OAT1 and OAT3 mediate the DDI between imipenem and cilastatin.Meanwhile,cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement.展开更多
基金funded by the Shenzhen Agricultural Development Special Fund(Fishery)Agricultural High-tech Project([2021]735)SAMR technical guarantee project(2023YJ22 and 2023YJ37)。
文摘Type 2 diabetes(T2D)presents a significant health challenge,underscoring the need for functional foods and nutraceutical hypoglycemic bioactive peptides for its prevention.This study investigates the potential of proteolytic hydrolysate from artificially cultivated Chinese giant salamander(CGS)meat,a rich protein source,as a preventive strategy for T2D.We produced a CGS meat hydrolysate(CGSh)and demonstrated its ability to inhibit the T2D drug target dipeptidyl peptidaseⅣ(DPP-Ⅳ)through in vitro assays.We identified 5 peptides(WRPPDH,WAPPSKD,IPDSPF,IPEMIF,and VPIAVPT)with high DPP-Ⅳinhibitory activity in CGSh,suggesting its potential antidiabetic effects.In vivo experiments showed that CGSh effectively reduced insulin resistance in mice induced with a high-fat diet,as evidenced by a slower increase in blood glucose levels and a decreased HOMA-IR index.16S rRNA sequencing analysis revealed that CGSh improved gut microbial homeostasis,promoting beneficial microorganisms and reducing harmful bacteria.Metabolomic analyses identified an increase in valeric acid levels and highlighted nine potential biomarker metabolites.By inhibiting metabolic pathways such as AGE-RAGE,CGSh might also prevent diabetic complications and reduce inflammation.These findings suggest that CGSh has a promising hypoglycemic effect,making it a potential functional food ingredient for T2D prevention and treatment.
基金supported by a grant from the National Natural Science Foundation of China (No. 81874324,81473280,U1608283)the Natural Science Foundation of Liaoning (No. 20170540293)Dalian Science and technology innovation fund (No. 2018J12SN065).
文摘This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma concentration-time curve(AUC)of cilastatin were significantly increased,while renal clearance and cumulative urinary excretion of cilastatin were decreased.At the same time,imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1(hOAT1)-HEK293 and human OAT3(hOAT3)-HEK293 cells.Probenecid,p-aminohippurate,and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1-and hOAT3-HEK 293 cells,respectively.The uptakes of imipenem and cilastatin in hOAT1-and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells.Moreover,the K m values of cilastatin were increased in the presence of imipenem with unchanged V max,indicating that imipenem inhibited the uptake of cilastatin in a competitive manner.When imipenem and cilastatin were co-administered,the level of imipenem was higher compared with imipenem alone both in vivo and in vitro.But,cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1(DPEP1)was silenced by RNAi technology in hOAT1-and hOAT3-HEK 293 cells.In conclusion,imipenem and cilastatin are the substrates of OAT1 and OAT3.OAT1 and OAT3 mediate the DDI between imipenem and cilastatin.Meanwhile,cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement.
