Journal
JOURNAL OF LIPID RESEARCH
Volume 51, Issue 6, Pages 1452-1463Publisher
ELSEVIER
DOI: 10.1194/jlr.M005363
Keywords
adipocytes; adipose tissue; diabetes; glucose; triglycerides
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK-075040, U24-DK-59637, DK-76769, DK59630]
- National Institutes of Health [T32-DK-007319]
Ask authors/readers for more resources
The aim of this study was to investigate the role of the cytosolic form of phosphoenolpyruvate carboxykinase (Pck1) in the development of insulin resistance. Previous studies have shown that the roles of Pck1 in white adipose tissue (WAT) in glyceroneogenesis and reesterification of free fatty acids (FFA) to generate triglyceride are vital for the prevention of diabetes. We hypothesized that insulin resistance develops when dysregulation of Pck1 occurs in the triglyceride/fatty acid cycle, which regulates lipid synthesis and transport between adipose tissue and the liver. We examined this by analyzing mice with a deletion of the PPAR gamma binding site in the promoter of Pck1 (PPARE(-/-)). This mutation reduced the fasting Pck1 mRNA expression in WAT in brown adipose tissue (BAT). To analyze insulin resistance, we performed hyperinsulinemic-euglycemic glucose clamp analyses. PPARE(-/-) mice were profoundly insulin resistant and had more FFA and glycerol released during the hyperinsulinemic-euglycemic clamp compared with wildtype mice (WT). Finally, we analyzed insulin secretion in isolated islets. We found a 2-fold increase in insulin secretion in the PPARE(-/-) mice at 16.7 mM glucose. Thus, the PPARE site in the Pck1 promoter is essential for maintenance of lipid metabolism and glucose homeostasis and disease prevention.-Millward, C. A., D. DeSantis, C-W. Hsieh, J. D. Heaney, S. Pisano, Y. Olswang, L. Reshef, M. Beidelschies, M. Puchowicz, and C. M. Croniger. Phosphoenolpyruvate carboxykinase (Pck1) helps regulate the triglyceride/fatty acid cycle and development of insulin resistance in mice. J. Lipid Res. 2010. 51: 1452-1463.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available