Horm Metab Res 2009; 41(10): 757-761
DOI: 10.1055/s-0029-1225363
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

In Vivo Knockdown of p85α with an Antisense Oligonucleotide Improves Insulin Sensitivity in Lep ob/ob and Diet-induced Obese Mice

M. W. Moriarty1 , C. E. McCurdy1 , R. C. Janssen1 , T. Shaw1 , J. W. Leitner2 , J. E. Friedman1 , 3 , B. Draznin2
  • 1Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA
  • 2Department of Medicine, University of Colorado Denver, Aurora, CO, USA
  • 3Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO, USA
Weitere Informationen

Publikationsverlauf

received 05.03.2009

accepted 27.05.2009

Publikationsdatum:
13. Juli 2009 (online)

Abstract

Phosphoinositide 3-kinase is a key signaling intermediate necessary for the metabolic actions of insulin. In this study, we assessed the effects of in vivo knockdown of the p85α subunit of phosphoinositide 3-kinase on insulin sensitivity, using an antisense oligonucleotide, in lean mice, diet-induced obese mice, and obese leptin-deficient Lep ob/ob mice. Mice were injected with either p85α-targeted antisense oligonucleotide or saline twice weekly for 4 weeks. Fasting levels of glycemia and insulinemia and insulin and glucose tolerance tests were used to determine insulin sensitivity. Western blot analysis and real-time polyacrylamide chain reaction were used to assess p85α protein and mRNA expression. In vivo administration of antisense oligonucleotide resulted in 50 and 60% knockdown of liver p85α protein and mRNA, respectively, in the lean, diet-induced obese and Lep ob/ob mice. This was associated with increased phosphoinositide 3-kinase activity and improved insulin sensitivity in diet-induced obese and Lep ob/ob mice. Thus, p85α could be an important therapeutic target to ameliorate insulin resistance.

References

Correspondence

M. W. Moriarty, MD 

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