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Facile synthesis of insulin fusion derivatives through sortase A ligation

Acta Pharmaceutica Sinica B 2021年第9期11卷 2719-2725页

作者： Maria M.Disotuar Jake A.Smith Jinze Li Steve Alam Nai-Pin Lin Danny Hung-Chieh Chou Department of Biochemistry School of MedicineUniversity of UtahSalt Lake CityUT 84112USA Division of Endocrinology and Diabetes Department of PediatricsSchool of MedicineStanford UniversityPalo AltoCA 94305USA

insulin derivatives such as insulin detemir and insulin degludec are *** and Drug Administration(FDA)-approved long-acting insulin currently used by millions of people with *** derivatives are modified in C-terminal B29 lysine to retain insulin *** and efficient methods for facile synthesis of insulin derivatives may lead to new discovery of therapeutic ***,we report a new method using sortase A(SrtA)-mediated ligation for the synthesis of insulin derivatives with high efficiency and functional group tolerance in the C-terminal B *** new insulin molecule(Ins-SA) with an SrtA-recognizing motif can be conjugated to diverse groups with N-terminal oligoglycines to generate new insulin *** further demonstrated that a new insulin derivative synthesized by this SrtA-mediated ligation shows strong cellular and in vivo *** enzymatic method can therefore be used for future insulin design and development.

关键词： Diabetes mellitus insulin synthesis Sortase A(SrtA)ligation Albumin-binding peptide SA21 Long-acting insulin

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Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

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Food Science and Human Wellness 2024年第3期13卷 1390-1401页

作者： Ting Liu Si Chen Yunhe Qu Lujuan Zheng Xiaoxuan Yang Shuhan Men Yuanning Wang Hanrui Ma Yifa Zhou Yuying Fan Engineering Research Center of Glycoconjugates Ministry of EducationJilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural DrugsSchool of Life SciencesNortheast Normal UniversityChangchun 130024China

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-*** pancreatic islets and enhancing insulin secretion has been therapeutic *** is the main type of polysaccharide from natural mushroom,which has potential medicinal ***,the antidiabetic property of mannogalactoglucan in T1DM has not been fully *** this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of *** and investigated the potential therapeutic value of AAMP-N in *** demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM ***-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in *** that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.

关键词： Mannogalactoglucan Mushroom Pancreatic islets insulin secretion insulin synthesis Unfolded protein response(UPR) Type 1 diabetes mellitus(T1DM)

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