scholarly journals Inhibition of insulin release by synthetic peptides shows that the H3 region at the C-terminal domain of syntaxin-1 is crucial for Ca2+- but not for guanosine 5′-[γ-thio]triphosphate-induced secretion

1996 ◽  
Vol 320 (1) ◽  
pp. 201-205 ◽  
Author(s):  
Franz MARTIN ◽  
Eva SALINAS ◽  
Jesús VAZQUEZ ◽  
Bernat SORIA ◽  
Juan A. REIG
Keyword(s):  
Insulin Release ◽  
Protein Interactions ◽  
Synthetic Peptides ◽  
Random Sequence ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Terminal Domain

Recently, we have described the presence and possible role of syntaxin in pancreatic β-cells by using monoclonal antibodies [F. Martin, F. Moya, L. M. Gutierrez, J. A. Reig, B. Soria (1995) Diabetologia 38, 860–863]. In order to characterize further the importance of specific domains of this protein, the functional role of a particular region of the syntaxin-1 molecule has now been investigated by using two synthetic peptides, SynA and SynB, corresponding to two portions of the H3 region at the C-terminal domain of the protein, residues 229–251 and 197–219 respectively. Functional experiments carried out in permeabilized pancreatic β-cells demonstrate that these peptides inhibit Ca2+- dependent insulin release in a dose-dependent manner. This effect is specific because peptides of the same composition but random sequence do not show the same effect. In contrast with this inhibitory effect on Ca2+-induced secretion, both peptides increase basal release. However, under the same conditions, SynA and SynB do not affect guanosine 5´-[γ-thio]triphosphate-induced insulin release. These results demonstrate that specific portions of the H3 region of syntaxin-1 are involved in critical protein–protein interactions specifically during Ca2+-induced insulin secretion.

scholarly journals Ca2+-Induced Ca2+ Release in the Pancreatic β-Cell: Direct Evidence of Endoplasmic Reticulum Ca2+ Release

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3565-3574 ◽  
Author(s):  
Thomas K. Graves ◽  
Patricia M. Hinkle
Keyword(s):  
Endoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Dependent Manner ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Release Channel ◽  
Voltage Gated ◽  
Carbamyl Choline ◽  
Dose Dependent

Abstract The role of the Ca2+-induced Ca2+ release channel (ryanodine receptor) in MIN6 pancreatic β-cells was investigated. An endoplasmic reticulum (ER)-targeted “cameleon” was used to report lumenal free Ca2+. Depolarization of MIN6 cells with KCl led to release of Ca2+ from the ER. This ER Ca2+ release was mimicked by treatment with the ryanodine receptor agonists caffeine and 4-chloro-m-cresol, reversed by voltage-gated Ca2+ channel antagonists and blocked by treatment with antagonistic concentrations of ryanodine. The depolarization-induced rise in cytoplasmic Ca2+ was also inhibited by ryanodine, which did not alter voltage-gated Ca2+ channel activation. Both ER and cytoplasmic Ca2+ changes induced by depolarization occurred in a dose-dependent manner. Glucose caused a delayed rise in cytoplasmic Ca2+ but no detectable change in ER Ca2+. Carbamyl choline caused ER Ca2+ release, a response that was not altered by ryanodine. Taken together, these results provide strong evidence that Ca2+-induced Ca2+ release augments cytoplasmic Ca2+ signals in pancreatic β-cells.

scholarly journals Long-Term Exposure of Pancreatic β-Cells to Palmitate Results in SREBP-1C-Dependent Decreases in GLP-1 Receptor Signaling via CREB and AKT and Insulin Secretory Response

Endocrinology ◽  
2016 ◽  
Vol 157 (6) ◽  
pp. 2243-2258 ◽  
Author(s):  
Annalisa Natalicchio ◽  
Giuseppina Biondi ◽  
Nicola Marrano ◽  
Rossella Labarbuta ◽  
Federica Tortosa ◽  
...  
Keyword(s):  
Protein Expression ◽  
Insulin Release ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Camp Response Element ◽  
Element Binding Protein ◽  
Viral Oncogene Homolog ◽  
Erk Kinase

The effects of prolonged exposure of pancreatic β-cells to high saturated fatty acids on glucagon-like peptide-1 (GLP-1) action were investigated. Murine islets, human pancreatic 1.1B4 cells, and rat INS-1E cells were exposed to palmitate for 24 hours. mRNA and protein expression/phosphorylation were measured by real-time RT-PCR and immunoblotting, respectively. Specific short interfering RNAs were used to knockdown expression of the GLP-1 receptor (Glp1r) and Srebf1. Insulin release was assessed with a specific ELISA. Exposure of murine islets, as well as of human and INS-1E β-cells, to palmitate reduced the ability of exendin-4 to augment insulin mRNA levels, protein content, and release. In addition, palmitate blocked exendin-4-stimulated cAMP-response element-binding protein and v-akt murine thymoma viral oncogene homolog phosphorylation, whereas phosphorylation of MAPK-ERK kinase-1/2 and ERK-1/2 was not altered. Similarly, RNA interference-mediated suppression of Glp1r expression prevented exendin-4-induced cAMP-response element-binding protein and v-akt murine thymoma viral oncogene homolog phosphorylation, but did not impair exendin-4 stimulation of MAPK-ERK kinase-1/2 and ERK-1/2. Both islets from mice fed a high fat diet and human and INS-1E β-cells exposed to palmitate showed reduced GLP-1 receptor and pancreatic duodenal homeobox-1 (PDX-1) and increased sterol regulatory element-binding protein (SREBP-1C) mRNA and protein levels. Furthermore, suppression of SREBP-1C protein expression prevented the reduction of PDX-1 and GLP-1 receptor levels and restored exendin-4 signaling and action. Finally, treatment of INS-1E cells with metformin for 24 h resulted in inhibition of SREBP-1C expression, increased PDX-1 and GLP-1 receptor levels, consequently, enhancement of exendin-4-induced insulin release. Palmitate impairs exendin-4 effects on β-cells by reducing PDX-1 and GLP-1 receptor expression and signaling in a SREBP-1C-dependent manner. Metformin counteracts the impairment of GLP-1 receptor signaling induced by palmitate.

Non-functional role of syntaxin 2 in insulin exocytosis by pancreatic β cells

1997 ◽  
Vol 15 (4) ◽  
pp. 237-242 ◽  
Author(s):  
Shinya Nagamatsu ◽  
Hiroki Sawa ◽  
Yoko Nakamichi ◽  
Yoshinori Kondo ◽  
Satsuki Matsushima ◽  
...  
Keyword(s):  
Functional Role ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Insulin Exocytosis

Role of Receptor Binding and Gene Transcription for Both of Stimulatory and Inhibitory Effects of Interleukin-1 In Pancreatic β-Cells

Autoimmunity ◽  
1992 ◽  
Vol 12 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Décio L. Eizirik ◽  
Daniel E. Tracey ◽  
Klaus Bendtzen ◽  
Stellan Sandler
Keyword(s):  
Gene Transcription ◽  
Receptor Binding ◽  
Interleukin 1 ◽  
Inhibitory Effects ◽  
Β Cells ◽  
Pancreatic Β Cells

Role Of Cyclic Amp In The Inhibition Of Human Platelet Functions By Quercetin, A Flav0N0Id That Potentiates PGI2 Effect

1981 ◽  
Author(s):  
J P Cazenave ◽  
A Beretz ◽  
A Stierlé ◽  
R Anton
Keyword(s):  
Maximum Level ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Pde Inhibitors ◽  
Pde Inhibition ◽  
Induced Aggregation ◽  
Camp Levels ◽  
Dose Dependent

Injury to the endothelium (END) and subsequent platelet (PLAT)interactions with the subEND are important steps in thrombosis and atherosclerosis. Thus,drugs that protect the END from injury and also inhibit PLAT function are of interest. It has been shown that some flavonoids(FLA), a group of compounds found in plants, prevent END desquamation in vivo, inhibit cyclic nucleotide phosphodiesterases(PDE)and inhibit PLAT function. We have studied the structure-activity relationships of 13 purified FLA on aggregation and secretion of 14c-5HT of prelabeled washed human PLAT induced by ADP, collagen(COLL) and thrombin(THR). All the FLA were inhibitors of the 3 agents tested. Quercetin(Q), was the second best after fisetin. It inhibited secretion and aggregation with I50 of 330µM against 0.1 U/ML.THR, 102µM against 5µM ADP and 40 µM against COLL. This inhibitory effect is in the range of that of other PDE inhibitors like dipyridamole or 3-isobutyl-l- methylxanthine. The aggregation induced by ADP, COLL and THR is at least mediated by 3 mechanisms that can be inhibited by increasing cAMP levels. We next investigated if Q, which is a PDE inhibitor of bovine aortic microsomes,raises PLAT cAMP levels. cAMP was measured by a protein-binding method. ADP- induced aggregation(5µM) was inhibited by PGI2 (0.1 and 0.5 nM) . Inhibition was further potentiated(l.7 and 3.3 times) by lOµM Q, which alone has no effect on aggregation. The basal level of cAMP(2.2 pmol/108PLAT) was not modified by Q (50 to 500µM). Using these concentrations of Q,the rise in cAMP caused by PGI2(0.1 and 0.5nM) was potentiated in a dose dependent manner. Q potentiated the effect of PGI2 on the maximum level of cAMP and retarded its breakdown. Thus Q and possibly other FLA could inhibit the interaction of PLAT with the components of the vessel wall by preventing END damage and by inhibiting PLAT function through a rise in cAMP secondary to PDE inhibition and potentiation of the effect of vascular PGI2 on PLAT adenylate cyclase.

Emerging Role of SUMO in Pancreatic β-Cells

2007 ◽  
Vol 39 (9) ◽  
pp. 658-664 ◽  
Author(s):  
A. Ehninger ◽  
H. Mziaut ◽  
M. Solimena
Keyword(s):  
Β Cells ◽  
Pancreatic Β Cells
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