Submitted on December 15, 2008
Revised on February 2, 2009
Accepted on March 5, 2009
Disengaging Insulin from Corticosterone: Roles of Each on Energy Intake and Disposition
James Philip Warne1, Susan F. Akana2, Abigail B Ginsberg, Hart F Horneman, Norman C. Pecoraro3, and Mary F Dallman2*
1 University of California San Francisco
2 University of California at San Francisco
3 UCSF
* To whom correspondence should be addressed. E-mail: Mary.Dallman{at}ucsf.edu.
Corticosterone and insulin play complex roles in the amount and composition of calories ingested, and the utilization and deposition of this energy. Understanding the interplay of these two hormones is complicated because increasing concentrations of corticosterone dose-dependently increase circulating insulin levels. We addressed individual contributions of each hormone by controlling, at steady-state levels, corticosterone (by adrenalectomy and exogenous replacement) and insulin (by streptozotocin-induced destruction of pancreatic 
-cells and exogenous replacement) across a spectrum of concentrations in rats, creating 8 hormonal combinations. 5 days after surgery, each group was subdivided into those receiving chow and those provided with chow, lard and sucrose (choice) for a further 5 days. During the choice/chow period, total calories ingested were stimulated by corticosterone and choice diet, and subject to a corticosterone-insulin interaction. Sucrose, but not lard, intake was stimulated by insulin. Body weight was stimulated by insulin, inhibited by high corticosterone and unaffected by diet. White adipose tissue depot weights were stimulated by insulin, corticosterone and diet. Plasma triglycerides, free fatty acids, total ketone bodies, glucose and glycerol were all significantly increased by corticosterone and the choice diet but inhibited by insulin. In contrast, plasma leptin was only increased by insulin and diet, plasma glucagon and liver glycogen only affected by insulin and liver triglycerides and arcuate nucleus proopiomelanocortin mRNA only influenced by diet. Collectively these data show that corticosterone and insulin determine the intake, form and compartmentalization of energy both independently and interactively.
