Improved transplantation outcome through delivery of DNA encoding secretion signal peptide-linked glucagon-like peptide-1 into mouse islets

2013 ◽  
Vol 26 (4) ◽  
pp. 443-452 ◽  
Author(s):  
Hee Young Chae ◽  
Minhyung Lee ◽  
Hyo Jeong Hwang ◽  
Hyun Ah Kim ◽  
Jun Goo Kang ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Dna Encoding ◽  
Secretion Signal ◽  
Secretion Signal Peptide ◽  
Mouse Islets ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Enhanced protection of Ins-1 β cells from apoptosis under hypoxia by delivery of DNA encoding secretion signal peptide-linked exendin-4

2009 ◽  
Vol 17 (3) ◽  
pp. 242-248 ◽  
Author(s):  
Hyun Ah Kim ◽  
Suyeon Lee ◽  
Jeong-Hyun Park ◽  
Sanghyun Lee ◽  
Byung-Wan Lee ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Dna Encoding ◽  
Β Cells ◽  
Secretion Signal ◽  
Secretion Signal Peptide

Functional enhancement of beta cells in transplanted pancreatic islets by secretion signal peptide-linked exendin-4 gene transduction

2012 ◽  
Vol 159 (3) ◽  
pp. 368-375 ◽  
Author(s):  
Jee-Heon Jeong ◽  
Simmyung Yook ◽  
Yoonsuk Jung ◽  
Bok-Hyeon Im ◽  
Minhyung Lee ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Beta Cells ◽  
Signal Peptide ◽  
Gene Transduction ◽  
Secretion Signal ◽  
Secretion Signal Peptide

scholarly journals The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression

2014 ◽  
Vol 34 (6) ◽  
Author(s):  
Yunjun Ge ◽  
Dehua Yang ◽  
Antao Dai ◽  
Caihong Zhou ◽  
Yue Zhu ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Receptor Expression ◽  
Hek293 Cells ◽  
Putative Signal Peptide ◽  
293 Cells ◽  
Class B ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

GLP-1R (glucagon-like peptide-1 receptor) mediates the ‘incretin effect’ and many other anti-diabetic actions of its cognate ligand, GLP-1 (glucagon-like peptide-1). It belongs to the class B family of GPCRs (G protein-coupled receptors) and possesses an N-terminal putative SP (signal peptide). It has been reported that this sequence is required for the synthesis of GLP-1R and is cleaved after receptor synthesis. In the present study, we conducted an in-depth exploration towards the role of the putative SP in GLP-1R synthesis. A mutant GLP-1R without this sequence was expressed in HEK293 cells (human embryonic kidney 293 cells) and displayed normal functionality with respect to ligand binding and activation of adenylate cyclase. Thus the putative SP does not seem to be required for receptor synthesis. Immunoblotting analysis shows that the amount of GLP-1R synthesized in HEK293 cells is low when the putative SP is absent. This indicates that the role of the sequence is to promote the expression of GLP-1R. Furthermore, epitopes tagged at the N-terminal of GLP-1R are detectable by immunofluorescence and immunoblotting in our experiments. In conclusion, the present study points to different roles of SP in GLP-1R expression which broadens our understanding of the functionality of this putative SP of GLP-1R and possibly other Class B GPCRs.

scholarly journals cAMP-Mediated and Metabolic Amplification of Insulin Secretion Are Distinct Pathways Sharing Independence of β-Cell Microfilaments

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4644-4654 ◽  
Author(s):  
Nizar I. Mourad ◽  
Myriam Nenquin ◽  
Jean-Claude Henquin
Keyword(s):  
Insulin Secretion ◽  
Actin Polymerization ◽  
Cytosolic Calcium ◽  
Actin Microfilaments ◽  
Insulin Granules ◽  
Adenylate Cyclase Stimulation ◽  
Mouse Islets ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Camp Levels

Abstract Insulin secretion is triggered by an increase in the cytosolic calcium concentration ([Ca2+]c) in β-cells. Ca2+-induced exocytosis of insulin granules can be augmented by metabolic amplification (unknown signals generated through glucose metabolism) or neurohormonal amplification (in particular cAMP mediated). Functional actin microfilaments are not required for metabolic amplification, but their possible role in cAMP-mediated amplification is unknown. It is also uncertain whether cAMP (generated in response to glucose) is implicated in metabolic amplification. These questions were addressed using isolated mouse islets. cAMP levels were increased by phosphodiesterase inhibition (with isobutylmethylxanthine) and adenylate-cyclase stimulation (with forskolin or glucagon-like peptide-1, 7-36 amide). Raising cAMP levels had no steady-state impact on actin polymerization in control islets. Neither disruption (depolymerization by latrunculin) nor stabilization (polymerization by jasplakinolide) of actin microfilaments was counteracted by cAMP. Both changes increased both phases of glucose- or tolbutamide-induced insulin secretion but did not prevent further amplification by cAMP. These large changes in secretion were not caused by changes in [Ca2+]c, which was only slightly increased by cAMP. Both phases of insulin secretion were larger in response to glucose than tolbutamide, although [Ca2+]c was lower. This difference in secretion, which reflects metabolic amplification, was independent of microfilaments, was not attributable to differences in cAMP, and persisted in presence of dibutyryl-cAMP or when cAMP levels were variably raised by isobutylmethylxanthine + forskolin or glucagon-like peptide-1, 7-36 amide. We conclude that metabolic and cAMP-mediated amplification of insulin secretion are distinct pathways that accelerate acquisition of release competence by insulin granules that can access exocytotic sites without intervention of microfilaments.

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