LAUSR

Gut hormones seem to regulate bone metabolism, but the mechanisms are unclear. New research suggests that glucose-dependent insulinotropic polypeptide (GIP) and xenin (hormones secreted by enteroendocrine K cells) are key factors in regulating several aspects of bone metabolism. Studies have shown that genetic deletion of the GIP receptor (GIPR) slightly increases trabecular bone mass. By contrast, mice given GIP analogues have increased trabecular bone mass. “It appears clear to us that a better understanding of the physiology of the GIP–GIPR pathway would lead to the development of second-generation medicines for the prevention and treatment of bone fragility,” explains author Guillaume mabilleau. The researchers found that ablation of the cells that produce GIP in mice (GIP–DT mice) did not alter bone strength or bone physiology. However, in mice that only lacked GIP (but retained expression of the other hormones produced by K cells; GIP–GFP–KI mice) trabecular bone mass was reduced, which was linked to increased bone fragility. These apparently conflicting results led the researchers to hypothesize that antagonistic actions of other gut hormones produced by K cells were involved in a feedback loop. Additional experiments revealed that xenin was involved in bone metabolism as part of a feedback loop that counteracts the action of GIP. “We also showed that other K cell-produced peptides, namely cholecystokinin, somatostatin and secretin, had very little or no effect on bone metabolism,” says mabilleau. The researchers suggest that their results support the development of GIP analogues for the treatment of bone disorders featuring low bone mass and increased bone fragility. “We are actively working on the development B O n E