New Scientist - July 30, 2007
Too much insulin may be bad for our health, turning the received wisdom about diabetes and Alzheimer’s disease on its head. Mice genetically engineered so that their brains don’t respond to insulin live longer and are less likely than normal mice to develop age-related diseases similar to Alzheimer’s.
Insulin plays a key role in encouraging the uptake and storage of glucose by cells. Its effects on the brain are less clear, but previous studies suggested that the hormone may stave off age-related degeneration.
"Everybody says insulin is good for you. It keeps cells alive," says Morris White of the Children’s Hospital in Boston. "But reviews are now starting to suggest that too much insulin can damage the brain and promote Alzheimer’s."
Last week he and his colleagues published research supporting that theory. They genetically engineered mice so that their brains didn’t produce Irs2, a key insulin receptor usually expressed throughout the body. The mice could eat as much food as they wanted and by 2 months of age all had become overweight and glucose intolerant. Like overweight humans, the mice had more insulin in their blood, but remarkably, says White, they did not develop diabetes or the mouse equivalent of Alzheimer’s and lived on average 14 percent longer than normal mice.
"By removing Irs2 from the brain, we protected it from the excess insulin," says White. This also seemed to lead to healthier brain activity (Science, DOI: 10.1126/science.1142179).
White suggests that insulin levels in the rest of the body could be irrelevant to the development of diabetes or Alzheimer’s, provided the brain is protected from excess insulin by removing its Irs2 receptors.
"Understanding how insulin is regulated in the brain could present exciting new treatment opportunities," says Clive Ballard, director of research at the U.K.’s Alzheimer’s Society. "A balanced diet and exercise are two suggested ways of keeping insulin levels low in the brain and will also help to reduce the risk of developing dementia."
Others remain skeptical. "It is definitely an exciting result," says Christian Holscher of the University of Ulster in Northern Ireland. "But you can’t get insulin desensitization by simply removing Irs2." There are other types of insulin receptor in the brain, he says, so the insulin signal will still get through.
Holscher also worries that removing Irs2 could harm health. "If you block insulin receptors in tissue cultures, the cells will die," he says. White agrees that it is vital that the insulin signal gets through to cells in some way. The key is achieving the right balance, he says. "Removing insulin receptors from the whole body is bad. But regulating Irs2 [in the brain] could be a good thing."
He suggests that controlling insulin activity could benefit people with Alzheimer’s because it drives protein synthesis and the disease is characterized by the build-up of an abnormal protein called beta-amyloid.