Aim To study the most stable pH value of endomorphin-1 solution and toestimate the shelf-life of EM-1 solution. Methods The content of EM-1 in its solution was determinedby HPLC, and stability was studied by accelerat...Aim To study the most stable pH value of endomorphin-1 solution and toestimate the shelf-life of EM-1 solution. Methods The content of EM-1 in its solution was determinedby HPLC, and stability was studied by accelerated tests. Results The most stable pH value of EM-1solution was observed. By the accelerated tests we obtained the Arrhe-nius relationship and thepharmacokinetic parameters. Conclusion The most stable pH value of EM-1 solution is 4.5 -4.8. Thet_(1/2)(25℃) is 45 d.展开更多
Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisati...Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisation through the formation of a disulfide bridge between the side chains of cysteine residues added to the sequence was explored. A further increase in stability was achieved through N-terminal modification with lipoamino acid and lactose succinamic acid, and the inclusion of D-amino acids. The latter also provided an alternative spatial arrangement of the aromatic side chains. The lipidated cyclic derivatives were insoluble in aqueous buffer, however, the cyclic peptides and glycopeptides showed greatly improved stability towards enzymatic degradation in human plasma.展开更多
Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The...Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 （GLP-1）, ghrelin and endomorphin-1 （EM-1） to the eastern and western style meals in patients with type 2 diabetes mellitus. Methods The study enrolled 57 patients with type 2 diabetes （20 men and 37 women, mean age （67.05±8.26） years）. Eastern style meal （meal A） and western style meal （meal B） were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before （0 hour） and after （2 hours） each diet. Results The delta （2h-0h） of C- peptide in meal A was significantly lower than that in meal B （P=0.0004）. C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A （P 〈0.0001, 〈0.0001, =0.001, =0.0004 respectively）. Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A （P=0.0005, 0.0079 respectively）. Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B （rA0h=0.7838, rB05=0.9368, rA25=0.7615, rB2h=0.9409, r A（2h-0h）=0.7531, rB（2h 05）=0.9980, respectively, P 〈0.0001）. Conclusion Western style meal （high fat and protein food） could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones （GLP-1, ghrelin） and brain peptide （EM-1） at the first phase of digestion.展开更多
文摘Aim To study the most stable pH value of endomorphin-1 solution and toestimate the shelf-life of EM-1 solution. Methods The content of EM-1 in its solution was determinedby HPLC, and stability was studied by accelerated tests. Results The most stable pH value of EM-1solution was observed. By the accelerated tests we obtained the Arrhe-nius relationship and thepharmacokinetic parameters. Conclusion The most stable pH value of EM-1 solution is 4.5 -4.8. Thet_(1/2)(25℃) is 45 d.
文摘Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisation through the formation of a disulfide bridge between the side chains of cysteine residues added to the sequence was explored. A further increase in stability was achieved through N-terminal modification with lipoamino acid and lactose succinamic acid, and the inclusion of D-amino acids. The latter also provided an alternative spatial arrangement of the aromatic side chains. The lipidated cyclic derivatives were insoluble in aqueous buffer, however, the cyclic peptides and glycopeptides showed greatly improved stability towards enzymatic degradation in human plasma.
基金supported by Natural Science Foundation of Anhui Province,No.1508085MH170 National Natural Science Foundation of China,No.81472656 Natural Science Foundation Project of Anhui Province Education Department,No.KJ2017A247
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81070677）. Conflict of interest： None.
文摘Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 （GLP-1）, ghrelin and endomorphin-1 （EM-1） to the eastern and western style meals in patients with type 2 diabetes mellitus. Methods The study enrolled 57 patients with type 2 diabetes （20 men and 37 women, mean age （67.05±8.26） years）. Eastern style meal （meal A） and western style meal （meal B） were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before （0 hour） and after （2 hours） each diet. Results The delta （2h-0h） of C- peptide in meal A was significantly lower than that in meal B （P=0.0004）. C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A （P 〈0.0001, 〈0.0001, =0.001, =0.0004 respectively）. Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A （P=0.0005, 0.0079 respectively）. Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B （rA0h=0.7838, rB05=0.9368, rA25=0.7615, rB2h=0.9409, r A（2h-0h）=0.7531, rB（2h 05）=0.9980, respectively, P 〈0.0001）. Conclusion Western style meal （high fat and protein food） could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones （GLP-1, ghrelin） and brain peptide （EM-1） at the first phase of digestion.
