Drug Discovery Opinion

Two back-to-back studies published in the July 23^rd issue of Cell, one from Columbia University Medical Center and the other from Johns Hopkins researchers, further the hypothesis that metabolic control and bone remodelling are inextricably linked. Both studies point to osteocalcin, a hormone released by bone, as a key mediator of this link.

The Johns Hopkins study used a conditional knock-out in mice to specifically suppress the expression of the insulin receptor in osteoblasts, the bone-forming cells of the skeletal system. As the mutant mice aged they became fat, had elevated blood sugar, and were glucose intolerant and resistant to insulin, mirroring the picture of diabetes in humans. The researchers found that the mutant mice had fewer osteoblasts, reduced bone formation and lower levels of circulating undercarboxylated osteocalcin (the active form of the hormone). The study showed that signalling via the insulin receptor in osteoblasts suppressed Twist2, an inhibitor of osteoblast development, and enhanced expression of osteocalcin, a mediator of insulin sensitivity and secretion.

The Columbia study links the complete bone remodelling process to energy regulation. Osteocalcin is released from osteoblasts predominantly in an inactive, carboxylated form. The researchers demonstrated that insulin signalling in osteoblasts stimulates release of inactive osteocalcin and activates osteoclasts, which activate the osteocalcin via decarboxylation in a bone-resorption-dependent manner.

The studies clearly have potential impact on human therapy, although significant questions remain. As yet the receptor for undercarboxylated osteocalcin is unknown, so the mechanism by with the hormone stimulates insulin release is unclear. Further work will be necessary to understand the interplay between skeletal- and metabolic-homeostasis in humans.

The two papers are previewed in Cell.

Related posts:

1. Liposomes can Deliver Wnt, Promote Bone Healing Wnt signalling plays an important role in the development and maintenance of many organs and tissues, and appears to be...
2. High Altitude Metabolism The cellular responses to low oxygen levels (hypoxia), as occurs at high altitude, are critical for survival. The transcription factor,...
3. New Basis for Link Between Sleep and Weight A number of human studies have linked lack of sleep to weight gain – decreased insulin sensitivity and glucose tolerance...
4. Another Way to Control GLP-1 The incretin, glucagon-like peptide-1 (GLP-1), is an intestinal hormone that stimulates production and release of insulin from pancreatic beta cells....
5. PPARγ– A New Twist in the Tale Obesity and related disorders such as diabetes have reached epidemic proportions. Although the anti-diabetic thiazolidinediones (glitazones) are effective insulin sensitizers,...

Related posts brought to you by Yet Another Related Posts Plugin.

 Email This Post

This entry was posted on Wednesday, July 28th, 2010 at 10:15 am and is filed under News. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.