Silencing of the FTO gene inhibits insulin secretion : An in vitro study using GRINCH cells

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Taneera , J , Prasad , R B , Dhaiban , S , Mohammed , A K , Haataja , L , Aryan , P , Hamad , M , Groop , L & Wollheim , C B 2018 , ' Silencing of the FTO gene inhibits insulin secretion : An in vitro study using GRINCH cells ' , Molecular and Cellular Endocrinology , vol. 472 , pp. 10-17 . https://doi.org/10.1016/j.mce.2018.06.003

Title: Silencing of the FTO gene inhibits insulin secretion : An in vitro study using GRINCH cells
Author: Taneera, Jalal; Prasad, Rashmi B.; Dhaiban, Sarah; Mohammed, Abdul Khader; Haataja, Leena; Aryan, Peter; Hamad, Mawieh; Groop, Leif; Wollheim, Claes B.
Contributor organization: Centre of Excellence in Complex Disease Genetics
Institute for Molecular Medicine Finland
Leif Groop Research Group
HUS Abdominal Center
Date: 2018-09-05
Language: eng
Number of pages: 8
Belongs to series: Molecular and Cellular Endocrinology
ISSN: 0303-7207
DOI: https://doi.org/10.1016/j.mce.2018.06.003
URI: http://hdl.handle.net/10138/306896
Abstract: Expression of fat mass and obesity-associated gene (FTO) and ADP-ribosylation factor-like 15 (ARL15) in human islets is inversely correlated with HbA(1c). However, their impact on insulin secretion is still ambiguous. Here in, we investigated the role of FTO and ARL15 using GRINCH (Glucose-Responsive Insulin-secreting C-peptide-modified Human proinsulin) clonal rat beta-cells. GRINCH cells have inserted GFP into the human C-peptide insulin gene. Hence, secreted CpepGFP served to monitor insulin secretion. mRNA silencing of FTO in GRINCH cells showed a significant reduction in glucose but not depolarization-stimulated insulin secretion, whereas ARL15 silencing had no effect. A significant down-regulation of insulin mRNA was observed in FTO knockdown cells. Type-2 Diabetic islets revealed a reduced expression of FTO mRNA. In conclusion, our data suggest that fluorescent CpepGFP released from GRINCH cells may serve as a convenient marker for insulin secretion. Silencing of FTO expression, but not ARL15, inhibits insulin secretion by affecting metabolic signaling.
Subject: FTO
ARL15
CHL1
Human islets
INS-832/13 cells
GRINCH cells
Type 2 diabetes
GLUCOSE-METABOLISM
ADULT OBESITY
HUMAN ISLETS
VARIANTS
EXPRESSION
ASSOCIATION
REGULATORS
CHILDHOOD
PATHWAYS
MUTATION
3121 General medicine, internal medicine and other clinical medicine
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion


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