TOO much insulin may be bad for our health, turning the received wisdom about diabetes and Alzheimer鈥檚 disease on its head. Mice genetically engineered so that their brains don鈥檛 respond to insulin live longer and are less likely than normal mice to develop age-related diseases similar to Alzheimer鈥檚.
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.
鈥淓verybody says insulin is good for you. It keeps cells alive,鈥� says Morris White of the Children鈥檚 Hospital in Boston. 鈥淏ut reviews are now starting to suggest that too much insulin can damage the brain and promote Alzheimer鈥檚.鈥�
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Last week he and his colleagues published research supporting that theory. They genetically engineered mice so that their brains didn鈥檛 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鈥檚 and lived on average 14 per cent longer than normal mice.
鈥淏y removing Irs2 from the brain, we protected it from the excess insulin,鈥� says White. This also seemed to lead to healthier brain activity (Science, ).
White suggests that insulin levels in the rest of the body could be irrelevant to the development of diabetes or Alzheimer鈥檚, provided the brain is protected from excess insulin by removing its Irs2 receptors.
鈥淯nderstanding how insulin is regulated in the brain could present exciting new treatment opportunities,鈥� says Clive Ballard, director of research at the UK鈥檚 Alzheimer鈥檚 Society. 鈥淎 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.鈥�
Others remain sceptical. 鈥淚t is definitely an exciting result,鈥� says Christian H枚lscher of the University of Ulster in Northern Ireland. 鈥淏ut you can鈥檛 get insulin desensitisation by simply removing Irs2.鈥� There are other types of insulin receptor in the brain, he says, so the insulin signal will still get through.
H枚lscher also worries that removing Irs2 could harm health. 鈥淚f you block insulin receptors in tissue cultures, the cells will die,鈥� 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. 鈥淩emoving insulin receptors from the whole body is bad. But regulating Irs2 [in the brain] could be a good thing.鈥�
He suggests that controlling insulin activity could benefit people with Alzheimer鈥檚 because it drives protein synthesis and the disease is characterised by the build-up of an abnormal protein called beta-amyloid.
