Joseph Williamson, M.D., a retired Washington University pathologist, read Raichle's 1988 study and was intrigued. Williamson, lead investigator for the other Washington University study appearing in PNAS, specializes in the effects of diabetes. In addition to elevating sugar levels throughout the body, diabetes also increases blood flow and can cause damage to nerves, retinas and kidneys.
Williamson was struck by a similarity between working muscle cells and cells of diabetic patients in regions likely to be damaged by the disease: both experienced increases in the ratio of two forms of a key energy-producing compound, nicotinamide adenine dinucleotide (NAD).
"Because of its role as the major carrier of electrons and protons from fuels for energy metabolism, NAD is strategically positioned -- even uniquely positioned -- to coordinate blood flow with energy metabolism in the resting cell, in the working cell and in disease states like diabetes and hypoxia," Williamson says.
When in use as a carrier of electrons and protons, NAD is converted to NADH (NAD plus H, or one atom of hydrogen). Williamson thought the ratio between these two forms of the compound (NADH/NAD) might be modulating blood flow.
Two other compounds involved in energy production, pyruvate and lactate, can affects cells' ratio of NADH to NAD. Williamson thought it might be possible to use this connection to test his theory. With colleagues at Washington University, he demonstrated in a 2001 rat study that blood flow to working skeletal muscle increased even more than normal after lactate injections, which increase the NADH/NAD ratio. Injections of pyruvate, which decrease the ratio, had the opposite effect. They also found the same results in brain regions that process sensory information from
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Contact: Michael C. Purdy
purdym@msnotes.wustl.edu
314-286-0122
Washington University School of Medicine
7-Jan-2004