Diphenylhydantoin protection of centpiperalone induced insulin release from β-cells

1980 ◽  
Vol 32 (1) ◽  
pp. 43-51
Author(s):  
Shyamal C. Maitra ◽  
Puvvada S.R. Murthi ◽  
Anil K. Rastogi ◽  
Surath K. Mukherjee
Keyword(s):  
Insulin Release ◽  
Β Cells

scholarly journals PDX1LOW MAFALOW β-cells contribute to islet function and insulin release

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Daniela Nasteska ◽  
Nicholas H. F. Fine ◽  
Fiona B. Ashford ◽  
Federica Cuozzo ◽  
Katrina Viloria ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Metabolic Stress ◽  
Human Islets ◽  
Islet Function ◽  
Β Cells ◽  
Β Cell ◽  
Ionic Fluxes ◽  
Transcriptomic Level ◽  
Adult Islet

AbstractTranscriptionally mature and immature β-cells co-exist within the adult islet. How such diversity contributes to insulin release remains poorly understood. Here we show that subtle differences in β-cell maturity, defined using PDX1 and MAFA expression, contribute to islet operation. Functional mapping of rodent and human islets containing proportionally more PDX1HIGH and MAFAHIGH β-cells reveals defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of PDX1HIGH and MAFAHIGH β-cells leads to dysregulation of gene pathways involved in metabolic processes. Using a chemogenetic disruption strategy, differences in PDX1 and MAFA expression are shown to depend on islet Ca2+ signaling patterns. During metabolic stress, islet function can be restored by redressing the balance between PDX1 and MAFA levels across the β-cell population. Thus, preserving heterogeneity in PDX1 and MAFA expression, and more widely in β-cell maturity, might be important for the maintenance of islet function.

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.

Calcium-independent potentiation of insulin release by cyclic AMP in single β-cells

Nature ◽  
1993 ◽  
Vol 363 (6427) ◽  
pp. 356-358 ◽  
Author(s):  
Carina Ämmälä ◽  
Frances M. Ashcroft ◽  
Patrik Rorsman
Keyword(s):  
Cyclic Amp ◽  
Insulin Release ◽  
Β Cells

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.

Insulin exocytosis in Goto-Kakizaki rat β-cells subjected to long-term glinide or sulfonylurea treatment

2008 ◽  
Vol 412 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Junko Kawai ◽  
Mica Ohara-Imaizumi ◽  
Yoko Nakamichi ◽  
Tadashi Okamura ◽  
Yoshihiro Akimoto ◽  
...  
Keyword(s):  
Insulin Release ◽  
Β Cells ◽  
Gk Rats ◽  
Insulin Granules ◽  
Long Term Treatment ◽  
Insulin Granule ◽  
Granule Motion ◽  
Insulin Exocytosis ◽  
First Phase Insulin Release

Sulfonylurea and glinide drugs display different effects on insulin granule motion in single β-cells in vitro. We therefore investigated the different effects that these drugs manifest towards insulin release in an in vivo long-term treatment model. Diabetic GK (Goto-Kakizaki) rats were treated with nateglinide, glibenclamide or insulin for 6 weeks. Insulin granule motion in single β-cells and the expression of SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins were then analysed. Perifusion studies showed that decreased first-phase insulin release was partially recovered when GK rats were treated with nateglinide or insulin for 6 weeks, whereas no first-phase release occurred with glibenclamide treatment. In accord with the perifusion results, TIRF (total internal reflection fluorescence) imaging of insulin exocytosis showed restoration of the decreased number of docked insulin granules and the fusion events from them during first-phase release for nateglinide or insulin, but not glibenclamide, treatment; electron microscopy results confirmed the TIRF microscopy data. Relative to vehicle-treated GK β-cells, an increased number of SNARE clusters were evident in nateglinide- or insulin-treated cells; a lesser increase was observed in glibenclamide-treated cells. Immunostaining for insulin showed that nateglinide treatment better preserved pancreatic islet morphology than did glibenclamide treatment. However, direct exposure of GK β-cells to these drugs could not restore the decreased first-phase insulin release nor the reduced numbers of docked insulin granules. We conclude that treatment of GK rats with nateglinide and glibenclamide varies in long-term effects on β-cell functions; nateglinide treatment appears overall to be more beneficial.

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