scholarly journals Loss of cell–cell and cell–substrate contacts in single pancreatic β‐cells divert insulin release to intracellular vesicular compartments

2020 ◽  
Vol 112 (12) ◽  
pp. 427-438
Author(s):  
Sanda Ljubicic ◽  
David Cottet‐Dumoulin ◽  
Domenico Bosco
Keyword(s):  
Insulin Release ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Cell Substrate ◽  
Cell Cell

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.

Tolbutamide and diazoxide modulate phospholipase C-linked Ca2+ signaling and insulin secretion in β-cells

2000 ◽  
Vol 278 (4) ◽  
pp. E639-E647 ◽  
Author(s):  
Christof Schöfl ◽  
Julia Börger ◽  
Thilo Mader ◽  
Mark Waring ◽  
Alexander von zur Mühlen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Phospholipase C ◽  
Insulin Release ◽  
Arginine Vasopressin ◽  
Bay K 8644 ◽  
Free Medium ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Activating Receptors

Arginine vasopressin (AVP), bombesin, and ACh increase cytosolic free Ca2+ and potentiate glucose-induced insulin release by activating receptors linked to phospholipase C (PLC). We examined whether tolbutamide and diazoxide, which close or open ATP-sensitive K+ channels (KATP channels), respectively, interact with PLC-linked Ca2+ signals in HIT-T15 and mouse β-cells and with PLC-linked insulin secretion from HIT-T15 cells. In the presence of glucose, the PLC-linked Ca2+ signals were enhanced by tolbutamide (3–300 μM) and inhibited by diazoxide (10–100 μM). The effects of tolbutamide and diazoxide on PLC-linked Ca2+ signaling were mimicked by BAY K 8644 and nifedipine, an activator and inhibitor of L-type voltage-sensitive Ca2+channels, respectively. Neither tolbutamide nor diazoxide affected PLC-linked mobilization of internal Ca2+ or store-operated Ca2+ influx through non-L-type Ca2+ channels. In the absence of glucose, PLC-linked Ca2+ signals were diminished or abolished; this effect could be partly antagonized by tolbutamide. In the presence of glucose, tolbutamide potentiated and diazoxide inhibited AVP- or bombesin-induced insulin secretion from HIT-T15 cells. Nifedipine (10 μM) blocked both the potentiating and inhibitory actions of tolbutamide and diazoxide on AVP-induced insulin release, respectively. In glucose-free medium, AVP-induced insulin release was reduced but was again potentiated by tolbutamide, whereas diazoxide caused no further inhibition. Thus tolbutamide and diazoxide regulate both PLC-linked Ca2+signaling and insulin secretion from pancreatic β-cells by modulating KATP channels, thereby determining voltage-sensitive Ca2+ influx.

scholarly journals Type 2 diabetes risk alleles in PAM impact insulin release from human pancreatic β-cells

2018 ◽  
Vol 50 (8) ◽  
pp. 1122-1131 ◽  
Author(s):  
Soren K. Thomsen ◽  
Anne Raimondo ◽  
Benoit Hastoy ◽  
Shahana Sengupta ◽  
Xiao-Qing Dai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Release ◽  
Diabetes Risk ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Risk Alleles

scholarly journals Phospholipase D1 Regulates Secretagogue-stimulated Insulin Release in Pancreatic β-Cells

2004 ◽  
Vol 279 (26) ◽  
pp. 27534-27541 ◽  
Author(s):  
William E. Hughes ◽  
Zehra Elgundi ◽  
Ping Huang ◽  
Michael A. Frohman ◽  
Trevor J. Biden
Keyword(s):  
Insulin Release ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Phospholipase D1

AMPA Receptors Regulate Exocytosis and Insulin Release in Pancreatic β Cells

Traffic ◽  
2012 ◽  
Vol 13 (8) ◽  
pp. 1124-1139 ◽  
Author(s):  
Zhen-Yong Wu ◽  
Li-Jun Zhu ◽  
Na Zou ◽  
Lidija K. Bombek ◽  
Chong-Yu Shao ◽  
...  
Keyword(s):  
Insulin Release ◽  
Ampa Receptors ◽  
Β Cells ◽  
Pancreatic Β Cells
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