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Rashmi Prasad

Rashmi Prasad

Assistant researcher

Rashmi Prasad

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

Author

  • Jalal Taneera
  • Rashmi B Prasad
  • Sarah Dhaiban
  • Abdul Khader Mohammed
  • Leena Haataja
  • Peter Arvan
  • Mawieh Hamad
  • Leif Groop
  • Claes B Wollheim

Summary, in English

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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Diabetic Complications
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2018

Language

English

Pages

10-17

Publication/Series

Molecular and Cellular Endocrinology

Volume

472

Document type

Journal article

Publisher

Elsevier

Topic

  • Medical Genetics
  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetic Complications

ISBN/ISSN/Other

  • ISSN: 0303-7207