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 delta (DGKdelta) expression and DGK activity in skeletal muscle from type 2 diabetic patients. In diabetic animals, reduced DGKdelta protein and DGK kinase activity were restored upon correction of glycemia. DGKdelta 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 DGKdelta haploinsufficient mice. We reveal a previously unrecognized role for DGKdelta in contributing to hyperglycemia-induced peripheral insulin resistance and thereby exacerbating the severity of type 2 diabetes. DGKdelta deficiency causes peripheral insulin resistance and metabolic inflexibility. These defects in glucose and energy homeostasis contribute to mild obesity later in life.
journal_name
Celljournal_title
Cellauthors
Chibalin AV,Leng Y,Vieira E,Krook A,Björnholm M,Long YC,Kotova O,Zhong Z,Sakane F,Steiler T,Nylén C,Wang J,Laakso M,Topham MK,Gilbert M,Wallberg-Henriksson H,Zierath JRdoi
10.1016/j.cell.2007.12.035subject
Has Abstractpub_date
2008-02-08 00:00:00pages
375-86issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(08)00056-1journal_volume
132pub_type
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