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Olga Kotova

Olga Kotova

Research engineer

Olga Kotova

Downregulation of Diacylglycerol Kinase Delta Contributes to Hyperglycemia-Induced Insulin Resistance

Author

  • Alexander V. Chibalin
  • Ying Leng
  • Elaine Vieira
  • Anna Krook
  • Marie Björnholm
  • Yun Chau Long
  • Olga Kotova
  • Zhihui Zhong
  • Fumio Sakane
  • Tatiana Steiler
  • Carolina Nylén
  • Jianjun Wang
  • Markku Laakso
  • Matthew K. Topham
  • Marc Gilbert
  • Harriet Wallberg-Henriksson
  • Juleen R. Zierath

Summary, in English

Type 2 (non-insulin-dependent) diabetes mellitus is a progressive metabolic disorder arising from genetic and environmental factors that impair beta cell function and insulin action in peripheral tissues. We identified reduced diacylglycerol kinase δ (DGKδ) expression and DGK activity in skeletal muscle from type 2 diabetic patients. In diabetic animals, reduced DGKδ protein and DGK kinase activity were restored upon correction of glycemia. DGKδ haploinsufficiency increased diacylglycerol content, reduced peripheral insulin sensitivity, insulin signaling, and glucose transport, and led to age-dependent obesity. Metabolic flexibility, evident by the transition between lipid and carbohydrate utilization during fasted and fed conditions, was impaired in DGKδ haploinsufficient mice. We reveal a previously unrecognized role for DGKδ in contributing to hyperglycemia-induced peripheral insulin resistance and thereby exacerbating the severity of type 2 diabetes. DGKδ deficiency causes peripheral insulin resistance and metabolic inflexibility. These defects in glucose and energy homeostasis contribute to mild obesity later in life.

Publishing year

2008-02-08

Language

English

Pages

375-386

Publication/Series

Cell

Volume

132

Issue

3

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology

Keywords

  • CELLBIO
  • HUMDISEASE
  • SIGNALING

Status

Published

ISBN/ISSN/Other

  • ISSN: 0092-8674