page 509). A lack of amylin production in type I (autoimmune) diabetics may explain the prominent bone loss in these individuals—a problem that amylin replacement therapy may alleviate.
When food is short, strengthening bone may not be the body's top priority. But when the food arrives it is time to build up bone mass. After food enters the digestive tract, amylin is cosecreted with insulin from pancreatic islet cells, but there is no known function for amylin in glucose metabolism. In the new work, the authors found that mice lacking either one or both copies of the amylin gene have normal appetites, but exhibit low bone mass and an increased number of bone-chewing osteoclasts. Ex vivo analysis of bone marrow macrophages from the mutant mice shows that amylin specifically regulates osteoclast differentiation.
Previous work had shown that amylin can bind to the calcitonin receptor in vitro, but the new study shows that heterozygous calcitonin receptor deletion increases bone mass, exactly opposite to the amylin knockout phenotype. Mice with heterozygous deletions in both calcitonin receptor and amylin genes show both increased osteoclast numbers and increased bone formation, with bone formation enjoying a slight edge.
Based on the results, Dacquin et al. propose that amylin, using a receptor other than the calcitonin receptor, regulates bone resorption by inhibiting the differentiation of osteoclasts. In patients with Type 1 diabetes, the absence of pancreatic islet cells should severely reduce the secretion of amylin, which would explain the bone loss associated with that disease. The authors are now trying to identify the real amylin receptor, and hope to use the new mouse model to search for therapies for diabetes-associated osteoporosis. ▪