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Review
. 2016 Nov;65(11):3225-3232.
doi: 10.2337/db16-0053.

Regulation of Glucose Handling by the Skeleton: Insights From Mouse and Human Studies

Jian-Min Liu  1 , Clifford J Rosen  2 , Patricia Ducy  3 , Stavroula Kousteni  4 , Gerard Karsenty  5
Affiliations
Review

Regulation of Glucose Handling by the Skeleton: Insights From Mouse and Human Studies

Jian-Min Liu et al. Diabetes. 2016 Nov.
No abstract available

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Figures

Figure 1
Figure 1
An integrative view on the role of bone in the regulation of energy homeostasis. The bioactive form of osteocalcin (ucOC) (1) binds to its Gprc6a receptor expressed on pancreatic β-cells (2) and intestinal epithelial cells (3), leading to the proliferation of β-cells and the release of GLP-1, thus stimulating insulin secretion (4). This action is counterbalanced by leptin signaling in the SNS: leptin crosses the blood-brain barrier (5) and binds to serotonergic neurons in the brain stem and inhibits serotonin synthesis (6), thereby diminishing the inhibitory effect of serotonin on sympathetic tone. With the increase of SNS activity, a larger amount of catecholamines can bind to Adrβ2 present on osteoblasts to increase Esp expression, thus decreasing insulin signaling on osteoblasts (7). Green lines indicate stimulation; red lines indicate inhibition. CCND1, cyclin D1.
Figure 2
Figure 2
Insulin signaling in osteoblasts facilitates the formation of metabolic active form of osteocalcin (ucOC). Insulin signaling on osteoblasts suppresses the expression of Twist2, a Runx2 inhibitor, thus favoring the production of osteocalcin (1), and, at the same time, it limits the production of OPG and enhances osteoclast activity (2), thus providing an acidic environment in the resorption lacuna for the formation of ucOC (3). Transcription factors forkhead box O (FoxO1) and activating transcription factor 4 (ATF4) act synergistically to suppress the bioactivity of osteocalcin by upregulating the expression of Esp (4), which can dephosphorylate the insulin receptor and inactivate its signaling on osteoblasts (5). Green lines indicate stimulation; red lines indicate inhibition. Gla-Oc, carboxylated osteocalcin.
See this image and copyright information in PMC

References

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