Skeletal IGF-1 Signaling Impacts Glucose and Energy Metabolism

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 199-233-Bone Biology
Basic/Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-209
Muriel Babey*1, Fong Chak1, Monique O'Leary2, Emmeline Academia2, Yongmei Wang1, Candice Tahminic1, Brian Kennedy2, Pankaj Kapahi2 and Daniel D Bikle1
1UCSF, San Francisco, CA, 2Buck Institute, Novato, CA
Insulin and insulin-like growth factor (IGF), their receptors, and IGF-binding proteins are important in the hormonal control of many metabolic and growth-related processes. Surprisingly, studies from mouse strains lacking the insulin receptor in two classical insulin target tissues, muscle and white fat, failed to demonstrate an impact on whole body glucose homeostasis. On the other hand we observe that knockdown of IGF-1 receptor in osteoblasts modulates glucose and energy metabolism in a diet dependent manner.

Under regular diet, glucose clearance was significantly increased in mice lacking the IGF-1 receptor in osteoblasts (IGF-1R OBKO, Cre-Recombinase driven by the 2.3 kb Collagen (α)I Type I promoter) compared to control mice. Glucose clearance was overall more improved in the female than in the male group. However, with the ingestion of a high fat diet, the differences in glucose clearance were not significant between IGF-1R OBKO mice and control mice for either gender. Female lean mass but not fat mass was significantly decreased in female IGF-1R OBKO mice compared to control mice ingesting a normal diet, and the high fat diet failed to increase the female fat mass in IGF-1R OBKO. In contrast, male lean mass was not decreased in the IGF-1R OBKO mice compared to control mice after a regular diet, and the high fat diet showed an increase in the male fat mass in IGF-1R OBKO mice over control mice.

Our preliminary results suggest that the early osteoblasts may have an important role in regulating both glucose and fat metabolism. The metabolic effects of IGF-1 signaling in osteoblasts are more pronounced in the female than in the male group in a diet dependent manner. Further metabolic tests will determine whether these effects are due to changes in endocrine factors such as insulin and osteocalcin and/or to alterations in physical activity, food intake or thermogenesis.

Nothing to Disclose: MB, FC, MO, EA, YW, CT, BK, PK, DDB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support:

This work is supported by a fellowship grant from the Novartis Foundation and the Janggen-Poehn Foundation awarded to Muriel Babey and by grant R01DK054793 from the National Institutes of Health awarded to Daniel D. Bikle.