A disordered thermostat  pg. 2

In the late 1970s, Daryl K. Granner, M.D., and his colleagues at the University of Iowa showed that insulin also turns down glucose production in the liver – another way of lowering blood glucose levels -- by inhibiting the gene for an enzyme called PEPCK.

“This was the first example of insulin affecting a specific gene,” says Granner, the Joe C. Davis Professor of Biomedical Science at Vanderbilt University Medical Center and former director of the Vanderbilt Diabetes Center. “There are probably now 200 of those examples.” For instance, there is evidence that insulin acts on the brain to inhibit appetite and help regulate weight.

“With mouse models, we’ve been able to understand the action of insulin and the role of each of these particular tissues a little bit more than we have any time in the past.” Dr. Mark A. Magnuson, professor of Molecular Physiology and Biophysics at Vanderbilt.
Photo by Dean Dixon
Other hormones are involved in the control of blood glucose. Glucagon, which is secreted by “alpha” cells in the islet, opposes the action of insulin and stimulates glucose production by the liver. So does cortisol, a stress hormone secreted by the adrenal glands on top of the kidneys.

This push-pull system is designed to keep blood glucose levels in balance, even after a feast, a fast or a flight from a predator.

Not enough blood glucose, a condition called hypoglycemia, can cause uncomfortable symptoms, including dizziness, confusion, heart palpitations and fatigue. It can lead to coma and death unless the glucose supply is replenished.

Too much blood glucose, the hallmark of diabetes, can damage the delicate inner lining of blood vessels, eventually leading to some of the major complications of diabetes – heart disease, kidney failure and blindness, caused by an overgrowth and leakage of tiny blood vessels in the retina of the eye.

“In type 2 diabetes there is an overproduction of glucose because these signals don’t work right,” says Alan D. Cherrington, Ph.D., holder of the Jacquelyn A. Turner and Dr. Dorothy J. Turner Chair in Diabetes Research at Vanderbilt who helped discover what glucagon does.

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