V2R structure and diabetes insipidus

For most audiences, the term "diabetes" conjures thoughts of high levels of blood glucose and of the symptoms that characterize diabetes mellitus. In the last few years, a spirited campaign spearheaded by the families of affected individuals has made progress in educating nonprofessional and medical communities about diabetes insipidus (DI), the other disease characterized by polyuria (i.e., diabetes). Much work lies ahead to find better treatments for this affliction, but the progress in molecular biology over the last years made possible the identification of the genetic defects underlying the inherited forms of the disease. Numerous cases of adult-onset DI are triggered by toxic damage to the kidneys that impairs the concentrating capacity of the nephrons by a nonspecific mechanism. In these pages I shall deal mostly with the inherited forms of the disease. Diabetes insipidus is characterized by the inability of the kidneys of affected individuals to produce concentrated urine (Morello and Bichet 2001). The elimination of large volumes of diluted urine (polyuria) and excessive thirst (polydipsia) are the chief symptoms of the disease. Although this condition and the hints that it was a hereditary disease were described at the end of the 19th century, it took almost 100 years to gain molecular knowledge about its etiology. A brief review of the important role played by vasopressin in the maintenance of body fluids will help the reader understand the severity of this disease.