Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance

Although insulin regulates metabolism in both brown and white adipocytes, t he role of these tissues in energy storage and utilization is quite differe nt. Recombination technology using the Cre-loxP approach allows inactivatio n of the insulin receptor in a tissue-specific manner. Mice lacking insulin receptors in brown adipocytes show an age-dependent loss of interscapular brown fat but increased expression of uncoupling protein-1 and -2. In paral lel, these mice develop an insulin-secretion defect resulting in a progress ive glucose intolerance, without insulin resistance. This model provides di rect evidence for not only a role for the insulin receptors in brown fat ad ipogenesis, the data also suggest a novel role of brown adipose tissue in t he regulation of insulin secretion and glucose homeostasis.