Silencing of the FTO gene inhibits insulin secretion: An in vitro study using GRINCH cells. (5th September 2018)

• Record Type: Journal Article
• Authors: Taneera, Jalal; Prasad, Rashmi B.; Dhaiban, Sarah; Mohammed, Abdul Khader; Haataja, Leena; Arvan, Peter; Hamad, Mawieh; Groop, Leif; Wollheim, Claes B.
• Is Part Of: Molecular and cellular endocrinology. Volume 472(2018)
• Page Start: 10
• Page End: 17
• Publication Date: 2018-09-05
• Subjects: FTO -- ARL15 -- CHL1 -- Human islets -- INS-832/13 cells -- GRINCH cells -- Type 2 diabetes; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.06.003
• Languages: English
• ISSNs: 0303-7207

Abstract

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 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. Highlights: GRINCH cells as a new tool to study pancreatic β-cell secretion facilitating drug screening. Knockdown of FTO expression inhibits glucose- but not potassium-stimulated insulin secretion. Knockdown of ARL15 expression has no impact on insulin secretion. FTO expression is lower in islets from T2D patients.