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Rashmi Prasad

Rashmi Prasad

Assistant researcher

Rashmi Prasad

A Central Role for GRB10 in Regulation of Islet Function in Man.

Author

  • Inga Prokopenko
  • Wenny Poon
  • Reedik Mägi
  • Rashmi Prasad
  • S Albert Salehi
  • Peter Almgren
  • Peter Osmark
  • Nabila Bouatia-Naji
  • Nils Wierup
  • Tove Fall
  • Alena Stančáková
  • Adam Barker
  • Vasiliki Lagou
  • Clive Osmond
  • Weijia Xie
  • Jari Lahti
  • Anne U Jackson
  • Yu-Ching Cheng
  • Jie Liu
  • Jeffrey R O'Connell
  • Paul A Blomstedt
  • Joao Fadista
  • Sami Alkayyali
  • Tasnim Dayeh
  • Emma Ahlqvist
  • Jalal Taneera
  • Cecile Lecoeur
  • Ashish Kumar
  • Ola Hansson
  • Karin B Hansson
  • Benjamin F Voight
  • Hyun Min Kang
  • Claire Levy-Marchal
  • Vincent Vatin
  • Aarno Palotie
  • Ann-Christine Syvänen
  • Andrea Mari
  • Michael N Weedon
  • Ruth J F Loos
  • Ken K Ong
  • Peter Nilsson
  • Bo Isomaa
  • Tiinamaija Tuomi
  • Nicholas J Wareham
  • Michael Stumvoll
  • Elisabeth Widen
  • Timo A Lakka
  • Claudia Langenberg
  • Anke Tönjes
  • Rainer Rauramaa
  • Johanna Kuusisto
  • Timothy M Frayling
  • Philippe Froguel
  • Mark Walker
  • Johan G Eriksson
  • Charlotte Ling
  • Peter Kovacs
  • Erik Ingelsson
  • Mark I McCarthy
  • Alan R Shuldiner
  • Kristi D Silver
  • Markku Laakso
  • Leif Groop
  • Valeriya Lyssenko

Summary, in English

Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Islet cell physiology
  • Neuroendocrine Cell Biology
  • Diabetes - Epigenetics
  • Division of Molecular Medicine and Gene Therapy
  • Internal Medicine - Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2014

Language

English

Publication/Series

PLoS Genetics

Volume

10

Issue

4

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Islet cell physiology
  • Neuroendocrine Cell Biology
  • Diabetes - Epigenetics
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1553-7404