One of the key components of this "intrinsic immunity" is encoded by the TRIM5 gene. This gene was discovered because the version of TRIM5 possessed by rhesus macaques allows them to resist HIV infection, whereas the human version does not. Instead, the human version appears to respond to evolutionarily older viruses that are related to now-extinct viruses that are resident in the human genome.

Previous studies had suggested that relatively few evolutionary changes in the TRIM5 protein were responsible for this difference in battling retroviral infection. This prompted the Malik and Emerman groups to screen human populations for slightly altered versions of TRIM5 that might be able to resist HIV infection.

Unexpectedly, the researchers found a single mutation in TRIM5 that impairs its ability to defend against retroviruses. This mutation occurs at a very high frequency in some ethnic groups, leading the authors to conclude that past periods in human history corresponding to relatively low levels of retroviral infections may have allowed impaired versions of retroviral defense genes--such as the hobbled version of TRIM5--to arise and thrive. As a consequence, the abundance of this impaired gene may have deleterious effects on the ability of present-day humans to ward off infections by both old and new retroviruses.

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The researchers infused the brains of the diabetic rats with a chemical that limits the function of an enzyme involved in the normal insulin response before injecting the animals with the hormone. Without the normal brain response to insulin, the hormone therapy's efficacy for reducing blood sugar fell by about 35%, Schwartz said. Furthermore, they found that gene therapy interventions designed to increase the brain's insulin response heightened the animals' response to therapy about 2-fold.

Strategies that target the molecules involved in the brain's response to insulin "may therefore prove beneficial in the management of diabetes in humans," the researchers said.

Differences in brain sensitivity to the insulin hormone might also help to explain the often "huge variation in insulin requirement" among otherwise comparable diabetes patients, Schwartz said.

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