scholarly journals High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets

2022 ◽  
Author(s):  
Hannah J MacMillan ◽  
Yahui Kong ◽  
Ezequiel Calvo-Roitberg ◽  
Laura C Alonso ◽  
Athma A Pai
Keyword(s):  
Cell Proliferation ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Molecular Mechanisms ◽  
Circular Rna ◽  
Beta Cell Proliferation ◽  
High Throughput Analysis ◽  
Exon 2 ◽  
Human Pancreatic Islets ◽  
Protective Allele

The antisense non-coding RNA in the INK locus (ANRIL) is a hotspot for genetic variants associated with cardiometabolic disease. We recently found increased ANRIL abundance in human pancreatic islets from donors with certain Type II Diabetes (T2D) risk-SNPs, including a T2D risk-SNP located within ANRIL exon 2 associated with beta cell proliferation. Recent studies have found that expression of circular species of ANRIL is linked to the regulation of cardiovascular phenotypes. Less is known about how the abundance of circular ANRIL may influence T2D phenotypes. Herein, we sequence circular RNA in pancreatic islets to characterize circular isoforms of ANRIL. We identify highly expressed circular ANRIL isoforms whose expression is correlated across dozens of individuals and characterize ANRIL splice sites that are commonly involved in back-splicing. We find that samples with the T2D risk allele in ANRIL exon 2 had higher ratios of circular to linear ANRIL compared to protective-allele carriers, and that higher circular:linear ANRIL was associated with decreased beta cell proliferation. Our study points to a combined involvement of both linear and circular ANRIL species in T2D phenotypes and opens the door for future studies of the molecular mechanisms by which ANRIL impacts cellular function in pancreatic islets.

scholarly journals Neural crest stem cells increase beta cell proliferation and improve islet function in co-transplanted murine pancreatic islets

Diabetologia ◽  
2009 ◽  
Vol 52 (12) ◽  
pp. 2594-2601 ◽  
Author(s):  
J. Olerud ◽  
N. Kanaykina ◽  
S. Vasilovska ◽  
D. King ◽  
M. Sandberg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Beta Cell ◽  
Neural Crest ◽  
Pancreatic Islets ◽  
Beta Cell Proliferation ◽  
Islet Function ◽  
Neural Crest Stem Cells

scholarly journals Chemical Methods to Induce Beta-Cell Proliferation

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Amedeo Vetere ◽  
Bridget K. Wagner
Keyword(s):  
Cell Proliferation ◽  
Beta Cell ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Proliferation ◽  
Cell Regeneration ◽  
Beta Cell Regeneration

Pancreatic beta-cell regeneration, for example, by inducing proliferation, remains an important goal in developing effective treatments for diabetes. However, beta cells have mainly been considered quiescent. This “static” view has recently been challenged by observations of relevant physiological conditions in which metabolic stress is compensated by an increase in beta-cell mass. Understanding the molecular mechanisms underlining these process could open the possibility of developing novel small molecules to increase beta-cell mass. Several cellular cell-cycle and signaling proteins provide attractive targets for high throughput screening, and recent advances in cell culture have enabled phenotypic screening for small molecule-induced beta-cell proliferation. We present here an overview of the current trends involving small-molecule approaches to induce beta-cell regeneration by proliferation.

scholarly journals Exendin-4 Promotes Beta Cell Proliferation via PI3k/Akt Signalling Pathway

2015 ◽  
Vol 35 (6) ◽  
pp. 2223-2232 ◽  
Author(s):  
Chaoxun Wang ◽  
Xiaopan Chen ◽  
Xiaoying Ding ◽  
Yanju He ◽  
Chengying Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Beta Cell ◽  
Molecular Mechanisms ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Cell Number ◽  
Beta Cell Proliferation ◽  
Proliferation In Vitro

Background/Aims: Prevention of diabetes requires maintenance of a functional beta-cell mass, the postnatal growth of which depends on beta cell proliferation. Past studies have shown evidence of an effect of an incretin analogue, Exendin-4, in promoting beta cell proliferation, whereas the underlying molecular mechanisms are not completely understood. Methods: Here we studied the effects of Exendin-4 on beta cell proliferation in vitro and in vivo through analysing BrdU-incorporated beta cells. We also analysed the effects of Exendin-4 on beta cell mass in vivo, and on beta cell number in vitro. Then, we applied specific inhibitors of different signalling pathways and analysed their effects on Exendin-4-induced beta cell proliferation. Results: Exendin-4 increased beta cell proliferation in vitro and in vivo, resulting in significant increases in beta cell mass and beta cell number, respectively. Inhibition of PI3K/Akt signalling, but not inhibition of either ERK/MAPK pathway, or JNK pathway, significantly abolished the effects of Exendin-4 in promoting beta cell proliferation. Conclusion: Exendin-4 promotes beta cell proliferation via PI3k/Akt signaling pathway.

13 - RGS9 Is Required for Glucose-Induced Beta-Cell Proliferation in Ex Vivo Pancreatic Islets

2020 ◽  
Vol 44 (7) ◽  
pp. S6
Author(s):  
Scott A. Campbell ◽  
Anais Szpigel ◽  
Caroline Tremblay ◽  
Julien Ghislain ◽  
Vincent Poitout
Keyword(s):  
Cell Proliferation ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Ex Vivo ◽  
Beta Cell Proliferation

Hormonal control of [beta]-cell proliferation in fetal ovine pancreatic isletsin vitro

2015 ◽  
Author(s):  
Shelley E Harris ◽  
Amy Kelly ◽  
Melissa A Davis ◽  
Miranda Anderson ◽  
Alison J Forhead ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Beta Cell ◽  
Hormonal Control ◽  
Beta Cell Proliferation

111-OR: Pancreatic Elastase Regulates Human Beta-Cell Proliferation via the Focal Adhesion and PAR2 Signaling Pathways

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 111-OR
Author(s):  
GIORGIO BASILE ◽  
AMEDEO VETERE ◽  
KA-CHEUK LIU ◽  
JIANG HU ◽  
OLOV ANDERSSON ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Beta Cell ◽  
Signaling Pathways ◽  
Focal Adhesion ◽  
Beta Cell Proliferation ◽  
Pancreatic Elastase ◽  
Human Beta Cell
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