Insulin signaling in osteoblasts mediates the activation of osteocalcin, which promotes insulin secretion in the pancreas and insulin sensitivity in other tissues. It is unknown if insulin resistance develops in bone in response to a high fat diet (HFD) and contributes to the disruption of glucose metabolism associated with the development of type 2 diabetes.
In this issue of the Journal of Clinical Investigation, Gerard Karsenty and colleagues of Columbia University determined that insulin resistance does develop in osteoblasts of mice fed a HFD and that this insulin resistance in bone cells contribute to the development of whole-body glucose intolerance through decreased circulation of active osteocalcin.
Osteoblast-specific insulin resistance resulted, in part, from increased ubiquitination and degradation of the insulin receptor in response to saturated fatty acids. In the accompanying Commentary, Ryan Riddle and Thomas Clemens of Johns Hopkins University indicate that understanding the interplay between the skeletal system and whole-body metabolism will be beneficial for a wide range of metabolic diseases.