Chronically high levels of insulin, as is found in many people with obesity and Type II diabetes, may block specific hormones that trigger energy release into the body, according to researchers at the University of California, San Diego (UCSD) School of Medicine. Their findings, which may point to new approaches to developing improved treatment options for the disease, will be published in the September 22 issue of the journal Nature.
The research team, led by Roger Y. Tsien, professor in UCSD’s Departments of Pharmacology and Chemistry and Biochemistry and a Howard Hughes Medical Institute investigator, found that high levels of insulin can block stress hormones known as catecholamines, which normally cause the release of cellular energy. Adrenaline is the best known example of a catecholamine. For normal metabolism to occur, the body needs a balanced input of insulin and catecholamines. One of the actions of insulin --, the main energy storage hormone, is to block activation of the protein kinase A (PKA) enzyme. After a meal, insulin levels go up, and the body stores energy primarily as triglycerides, or fat, in adipose tissue to be used later. When energy is needed, catecholamine triggers activation of PKA, and energy is released. But in people with Type II diabetes, the hormonal balance has been thrown off, because the body continues to produce and store more triglyceride instead of breaking down the fat as released energy.
“Somehow, insulin knows how to specifically block catecholamine-induced PKA, but not other molecules,” said Christopher Hupfeld, assistant professor of Medicine in the UCSD Division of Endocrinology and Metabolism and a co-author of the paper. “When the body has a constantly high level of insulin, this energy- release stimulus is lost.”
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