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Metabolism, memory, and the role of insulin in the brain

Gaining new insights into the link between diabetes and higher risk of dementia, scientists discovered, in research in mice, that insulin and the related hormone IGF-1 act in multiple parts of the brain to regulate blood sugar levels, memory, and other vital mind and body processes. Insulin and IGF-1 transmit critical biological signals, and prior research showed that impaired insulin and IGF-1 signaling in the brain is associated with diabetes, obesity, and potentially increased risk for Alzheimer’s disease and other cognitive problems. But much remains unknown.

To identify areas of the brain important for insulin and IGF-1 control of metabolism and cognitive functions, the researchers generated two groups of mice with reduced signaling by these hormones in specific regions of the brain—the hippocampus and central amygdala, respectively—and examined the effects. They found that, in mice with insulin/IGF-1 signaling deficiencies in either of these brain regions, blood glucose (sugar) levels rose above normal. Mice with these deficiencies in the central amygdala also could not maintain normal body temperature in a cold environment. From additional experiments, they determined that this effect was likely due to disrupted signaling along nerves that connect the brain to brown fat tissue, which generates heat. Investigating other effects, the researchers found that, compared to normal mice, those with insulin and IGF-1 signaling deficiencies in either of these brain regions did not differentiate between new and familiar objects, and they displayed anxiety-like behaviors. Mice with signaling deficiencies in the hippocampus were also much slower in learning to navigate their way through a maze and had more trouble remembering the route later. In their experiments, the researchers used only male mice to explore the role of insulin/IGF-1 signaling in the hippocampus, and only female mice in studies of the central amygdala. Thus, it is not yet clear whether some of the metabolic and cognitive effects reflect distinct functions of the two brain regions, differences between males and females, or both.

The results from this research in mice illuminate critical roles of the hormones insulin and IGF 1 in multiple areas of the brain and yield new insights into the connections between insulin action, metabolism, learning and memory, and anxiety-like behavior. These findings may lead to new ideas for therapies in humans not only for diabetes and obesity, but also for Alzheimer’s disease and other dementias.

Soto M, Cai W, Konishi M, and Kahn CR. Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavior. Proc Natl Acad Sci USA 116: 6379-6384, 2019.

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