In order to improve the life quality of diabetic patients,it is very important to develop rapid-acting insulin formulations that can mimic the physiological meal-time secretion profile of insulin in healthy people.Alt...In order to improve the life quality of diabetic patients,it is very important to develop rapid-acting insulin formulations that can mimic the physiological meal-time secretion profile of insulin in healthy people.Although several insulin analogues have been designed to provide postprandial glycemic control,still there are some serious disadvantages.A supramolecular strategy is presented here to inhibit insulin aggregation and improve its bioactivity by using Cp1-11 peptide.As a fragment of C-peptide in proinsulin,Cp1-11 peptide was found to influence insulin oligomerization by supramolecular interactions.This work demonstrates that the Cp1-11 peptide can interact with oligomeric insulin and facilitate its disaggregation into the physiologically active monomeric form.Computer simulation indicates that Cp1-11 can insert into the space between the C-terminal tail and the N-terminal helix of the B-chain of insulin,causing dissociation of the insulin dimer.The supramolecular assembly of Cp1-11 and insulin can improve the bioavailability and therapeutic effect of insulin on the control of in vivo blood glucose levels.These results suggest that Cp1-11 peptide can modulate the intermolecular interaction of aggregated insulin and prevent the transition from monomeric to multimeric states,and shows great potential for the development of an effective rapid-acting strategy to treat diabetes.展开更多
基金supported by National Natural Science Foundation of China (21534008,51322303 and 21174088)Program for Changjiang Scholars and Innovative Research Team in University (IRT_15R48)State Key Laboratory of Polymer Materials Engineering (Grant No.sklpme2017-2-02).
文摘In order to improve the life quality of diabetic patients,it is very important to develop rapid-acting insulin formulations that can mimic the physiological meal-time secretion profile of insulin in healthy people.Although several insulin analogues have been designed to provide postprandial glycemic control,still there are some serious disadvantages.A supramolecular strategy is presented here to inhibit insulin aggregation and improve its bioactivity by using Cp1-11 peptide.As a fragment of C-peptide in proinsulin,Cp1-11 peptide was found to influence insulin oligomerization by supramolecular interactions.This work demonstrates that the Cp1-11 peptide can interact with oligomeric insulin and facilitate its disaggregation into the physiologically active monomeric form.Computer simulation indicates that Cp1-11 can insert into the space between the C-terminal tail and the N-terminal helix of the B-chain of insulin,causing dissociation of the insulin dimer.The supramolecular assembly of Cp1-11 and insulin can improve the bioavailability and therapeutic effect of insulin on the control of in vivo blood glucose levels.These results suggest that Cp1-11 peptide can modulate the intermolecular interaction of aggregated insulin and prevent the transition from monomeric to multimeric states,and shows great potential for the development of an effective rapid-acting strategy to treat diabetes.
