JCI table of contents: Dec. 21, 2006
BONE BIOLOGY: p62 mutations can't go all the way in Paget disease
Paget disease is a bone disease that results in enlarged bones and causes bone pain, arthritis, deformities, and fractures. It mostly affects individuals over the age of 40 and has a hereditary component. One gene that is mutated in approximately one third of patients with hereditary Padget disease is p62 (sequestosome 1). However, it has not been clear whether mutations (such as the common p62P392L mutation) in this gene actually cause Paget disease.
In a study appearing online on December 21, in advance of publication in the January print issue of the Journal of Clinical Investigation, Noriyoshi Kurihara and colleagues from the VA Pittsburgh Healthcare System show that expression of the p62P392L mutation causes abnormal development of human bone cells in vitro and mouse bone cells in vivo but does not cause a Padget-like disease in mice. Specifically, expression of p62P392L in the precursors of human bone cells known as osteoclasts (the cells that destroy bone) caused them to be more responsive to factors that drive osteoclast development. Similarly, expression of p62P392L in osteoclast-lineage cells in mice resulted in increased numbers of osteoclasts. Although increased numbers of osteoclasts is a feature of Paget disease, it is not the full range of characteristics. This study therefore suggests that although mutations in p62 predispose an individual to developing Paget disease, other factors are required for the full development of Paget disease.
TITLE: Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease
VA Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Phone: (412) 688-6000 ext. 81-4990; Fax: (412) 688-6960; E-mail: [email protected]
View the PDF of this article at: https://www.the-jci.org/article.php?id=28267
METABOLIC DISEASE: Expanding our knowledge about expanding waistlines
The body ensures a constant level of energy is available to all of its cells through a complex system that includes regulating how much food we eat, how much of the digested food we absorb, how much of the digested food we store away, and how much of our energy store we release for use. If this balance is upset, individuals can become obese and develop type 2 diabetes. Two hormones produced by the gut, GIP and GLP1R, are involved in this process and are known to help control the amount of insulin (the hormone that causes energy in the form of glucose to be stored) released by the pancreas. But now, new roles for GIP and GLP1R outside the pancreas have been identified, in mice, by researchers from the University of Toronto.
In a study appearing online on December 21, in advance of publication in the January print issue of the Journal of Clinical Investigation, Daniel Drucker and colleagues used mice lacking either the receptor for GIP, the receptor for GLP1R or both receptors to show that the effects of GIP and GLP1R on energy levels are not restricted to the pancreas. GLP1R was shown to decrease energy expenditure by altering the functions of cells in the brain and GIP was shown to enhance energy storage as fat and reduce energy expenditure by altering the functions of cells in the adipose tissue (fat tissue) and brain. This study increases our understanding of the function of these two hormones and might influence the development of drugs designed to target these hormones for the treatment of type 2 diabetes.
TITLE: Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure
Daniel J. Drucker
University of Toronto, Toronto, Ontario, Canada.
Phone: (416) 361-2661; Fax: (416) 361-2669; E-mail: [email protected]
View the PDF of this article at: https://www.the-jci.org/article.php?id=25483
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