Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/121768
Title: MOLECULAR MECHANISM OF GLP-1 POTENTIATED INSULIN GRANULE EXOCYTOSIS
Authors: NEHA SHRESTHA
Keywords: Exocytosis, Insulin, GLP-1, Synaptotagmin, Rabphilin
Issue Date: 3-Aug-2015
Citation: NEHA SHRESTHA (2015-08-03). MOLECULAR MECHANISM OF GLP-1 POTENTIATED INSULIN GRANULE EXOCYTOSIS. ScholarBank@NUS Repository.
Abstract: GLUCAGON-LIKE PEPTIDE-1 (GLP-1) BASED DRUGS ARE WIDELY USED TO POTENTIATE INSULIN SECRETION AND IMPROVE METABOLIC CONTROL IN DIABETICS; HOWEVER, MOLECULAR MECHANISMS UNDERLYING GLP-1 POTENTIATION OF INSULIN SECRETION REMAIN UNCLEAR. PHOSPHORYLATION OF SYNAPTOTAGMIN7 (SYT7) BY PKA IS ESSENTIAL FOR GLP-1 POTENTIATION OF INSULIN RELEASE. USING PROTEOMICS APPROACH, WE FOUND THAT THE PHOSPHOMIMETIC FORM OF SYT7 EXHIBITS ENHANCED BINDING TO RABPHILIN3A (RPH3A). KNOCKDOWN OF ENDOGENOUS RPH3A FROM MIN6 CELLS DIMINISHED FORSKOLIN INDUCED INSULIN RELEASE WHILE OVEREXPRESSION OF PHOSPHOMIMETIC RPH3A (S234E) IN MOUSE ISLETS ENHANCED GLP-1 MEDIATED INSULIN SECRETION. INTERESTINGLY, MYOSIN VA- A MOTOR PROTEIN, ALSO COIMMUNOPRECIPITATED WITH SYT7 AND RPH3A UPON ACTIVATION OF PKA SIGNALING. KNOCKDOWN OF MYOVA DIMINISHED FORSKOLIN INDUCED INSULIN RELEASE. TOGETHER, OUR RESULTS SUGGEST THAT PHOSPHORYLATION OF SYT7 BY GLP-1 PROMOTES INSULIN GRANULE EXOCYTOSIS BY ENHANCING GRANULE TRANSLOCATION VIA ITS IN
URI: http://scholarbank.nus.edu.sg/handle/10635/121768
Appears in Collections:Ph.D Theses (Open)

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