Downregulation of Diacylglycerol Kinase Delta Contributes to Hyperglycemia-Induced Insulin Resistance
(2008) In Cell 132(3). p.375-386- Abstract
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,... (More)
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.
(Less)
- author
- publishing date
- 2008-02-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CELLBIO, HUMDISEASE, SIGNALING
- in
- Cell
- volume
- 132
- issue
- 3
- pages
- 12 pages
- publisher
- Cell Press
- external identifiers
-
- scopus:38849090672
- pmid:18267070
- ISSN
- 0092-8674
- DOI
- 10.1016/j.cell.2007.12.035
- language
- English
- LU publication?
- no
- id
- ccdf9ccd-10d9-4bcc-80b2-8c5911f5651a
- date added to LUP
- 2019-06-03 13:34:40
- date last changed
- 2024-08-21 21:16:31
@article{ccdf9ccd-10d9-4bcc-80b2-8c5911f5651a, abstract = {{<p>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.</p>}}, author = {{Chibalin, Alexander V. and Leng, Ying and Vieira, Elaine and Krook, Anna and Björnholm, Marie and Long, Yun Chau and Kotova, Olga and Zhong, Zhihui and Sakane, Fumio and Steiler, Tatiana and Nylén, Carolina and Wang, Jianjun and Laakso, Markku and Topham, Matthew K. and Gilbert, Marc and Wallberg-Henriksson, Harriet and Zierath, Juleen R.}}, issn = {{0092-8674}}, keywords = {{CELLBIO; HUMDISEASE; SIGNALING}}, language = {{eng}}, month = {{02}}, number = {{3}}, pages = {{375--386}}, publisher = {{Cell Press}}, series = {{Cell}}, title = {{Downregulation of Diacylglycerol Kinase Delta Contributes to Hyperglycemia-Induced Insulin Resistance}}, url = {{http://dx.doi.org/10.1016/j.cell.2007.12.035}}, doi = {{10.1016/j.cell.2007.12.035}}, volume = {{132}}, year = {{2008}}, }