Advanced

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

Taneera, Jalal LU ; Prasad, Rashmi B LU ; Dhaiban, Sarah; Mohammed, Abdul Khader; Haataja, Leena; Arvan, Peter; Hamad, Mawieh; Groop, Leif LU and Wollheim, Claes B LU (2018) In Molecular and Cellular Endocrinology 472. p.10-17
Abstract

Expression of fat mass and obesity-associated gene (FTO) and ADP-ribosylation factor-like 15 (ARL15) in human islets is inversely correlated with HbA1c. 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 β-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... (More)

Expression of fat mass and obesity-associated gene (FTO) and ADP-ribosylation factor-like 15 (ARL15) in human islets is inversely correlated with HbA1c. 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 β-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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular and Cellular Endocrinology
volume
472
pages
10 - 17
publisher
Elsevier
ISSN
1872-8057
DOI
language
English
LU publication?
yes
id
9d8615d1-608c-4824-aa69-926b3941cddd
date added to LUP
2018-06-12 21:04:52
date last changed
2018-06-13 14:38:24
@article{9d8615d1-608c-4824-aa69-926b3941cddd,
  abstract     = {<p>Expression of fat mass and obesity-associated gene (FTO) and ADP-ribosylation factor-like 15 (ARL15) in human islets is inversely correlated with HbA1c. 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 β-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.</p>},
  author       = {Taneera, Jalal and Prasad, Rashmi B and Dhaiban, Sarah and Mohammed, Abdul Khader and Haataja, Leena and Arvan, Peter and Hamad, Mawieh and Groop, Leif and Wollheim, Claes B},
  issn         = {1872-8057},
  language     = {eng},
  pages        = {10--17},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Endocrinology},
  title        = {Silencing of the FTO gene inhibits insulin secretion : An in vitro study using GRINCH cells},
  url          = {http://dx.doi.org/},
  volume       = {472},
  year         = {2018},
}