scholarly journals Induction of β-Cell Rest by a Kir6.2/SUR1-Selective KATP-Channel Opener Preserves β-Cell Insulin Stores and Insulin Secretion in Human Islets Cultured at High (11 mM) Glucose

2004 ◽  
Vol 89 (2) ◽  
pp. 795-805 ◽  
Author(s):  
Robert A. Ritzel ◽  
John B. Hansen ◽  
Johannes D. Veldhuis ◽  
Peter C. Butler
Keyword(s):  
Insulin Secretion ◽  
Katp Channel ◽  
Human Islets ◽  
Β Cell ◽  
Channel Opener ◽  
Katp Channel Opener

Diabetes prevention by a novel β cell-selective KATP channel opener, NNC55-0118, in OLETF rat

2000 ◽  
Vol 50 ◽  
pp. 383
Author(s):  
Toru Aizawa ◽  
John B Hansen ◽  
Richard D Carr ◽  
Christian L Brand ◽  
Mitsuhisa Komatsu ◽  
...  
Keyword(s):  
Katp Channel ◽  
Diabetes Prevention ◽  
Β Cell ◽  
Channel Opener ◽  
Katp Channel Opener ◽  
Oletf Rat

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 The regulator of G-protein signaling RGS16 promotes insulin secretion and β-cell proliferation in rodent and human islets

2016 ◽  
Vol 5 (10) ◽  
pp. 988-996 ◽  
Author(s):  
Kevin Vivot ◽  
Valentine S. Moullé ◽  
Bader Zarrouki ◽  
Caroline Tremblay ◽  
Arturo D. Mancini ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
G Protein ◽  
Human Islets ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Β Cell

Interaction between thiol-modifying agents and P1075, a KATP channel opener, in rat isolated aorta

1997 ◽  
Vol 356 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Claudia Linde ◽  
Cornelia Löffler ◽  
Christina Kessler ◽  
U. Quast
Keyword(s):  
Katp Channel ◽  
Channel Opener ◽  
Isolated Aorta ◽  
Katp Channel Opener

scholarly journals Human EndoC-βH1 β-cells form pseudoislets with improved glucose sensitivity and enhanced GLP-1 signaling in the presence of islet-derived endothelial cells

2018 ◽  
Vol 314 (5) ◽  
pp. E512-E521 ◽  
Author(s):  
Michael G. Spelios ◽  
Lauren A. Afinowicz ◽  
Regine C. Tipon ◽  
Eitan M. Akirav
Keyword(s):  
Endothelial Cells ◽  
Insulin Secretion ◽  
Cell Biology ◽  
Three Dimensional ◽  
Cell Types ◽  
Human Islets ◽  
Glucose Sensing ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Levels

Three-dimensional (3D) pseudoislets (PIs) can be used for the study of insulin-producing β-cells in free-floating islet-like structures similar to that of primary islets. Previously, we demonstrated the ability of islet-derived endothelial cells (iECs) to induce PIs using murine insulinomas, where PI formation enhanced insulin production and glucose responsiveness. In this report, we examined the ability of iECs to spontaneously induce the formation of free-floating 3D PIs using the EndoC-βH1 human β-cell line murine MS1 iEC. Within 14 days, the coculturing of both cell types produced fully humanized EndoC-βH1 PIs with little to no contaminating murine iECs. The size and shape of these PIs were similar to primary human islets. iEC-induced PIs demonstrated reduced dysregulated insulin release under low glucose levels and higher insulin secretion in response to high glucose and exendin-4 [a glucagon-like peptide-1 (GLP-1) analog] compared with monolayer cells cultured alone. Interestingly, iEC-PIs were also better at glucose sensing in the presence of extendin-4 compared with PIs generated on a low-adhesion surface plate in the absence of iECs and showed an overall improvement in cell viability. iEC-induced PIs exhibited increased expression of key genes involved in glucose transport, glucose sensing, β-cell differentiation, and insulin processing, with a concomitant decrease in glucagon mRNA expression. The enhanced responsiveness to exendin-4 was associated with increased protein expression of GLP-1 receptor and phosphokinase A. This rapid coculture system provides an unlimited number of human PIs with improved insulin secretion and GLP-1 responsiveness for the study of β-cell biology.

scholarly journals Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Francesco Volta ◽  
M. Julia Scerbo ◽  
Anett Seelig ◽  
Robert Wagner ◽  
Nils O’Brien ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Homeostasis ◽  
Basal Body ◽  
Primary Cilia ◽  
Epithelial To Mesenchymal Transition ◽  
Human Islets ◽  
Β Cells ◽  
Β Cell ◽  
Mesenchymal Transition ◽  
Glucose Levels

Abstract Diabetes mellitus affects one in eleven adults worldwide. Most suffer from Type 2 Diabetes which features elevated blood glucose levels and an inability to adequately secrete or respond to insulin. Insulin producing β-cells have primary cilia which are implicated in the regulation of glucose metabolism, insulin signaling and secretion. To better understand how β-cell cilia affect glucose handling, we ablate cilia from mature β-cells by deleting key cilia component Ift88. Here we report that glucose homeostasis and insulin secretion deteriorate over 12 weeks post-induction. Cilia/basal body components are required to suppress spontaneous auto-activation of EphA3 and hyper-phosphorylation of EphA receptors inhibits insulin secretion. In β-cells, loss of cilia/basal body function leads to polarity defects and epithelial-to-mesenchymal transition. Defective insulin secretion from IFT88-depleted human islets and elevated pEPHA3 in islets from diabetic donors both point to a role for cilia/basal body proteins in human glucose homeostasis.

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