The UVa team believes this compound, called D-chiro-Inositol-Galactosamine, or INS2, acts as a messenger inside cells to switch on enzymes that regulate blood sugar, taking glucose from the bloodstream into the liver and muscles where it is stored. INS2 is naturally occurring in the body and is found in human blood. “We believe this molecule works by sending a message inside the cell to respond to insulin, which helps cells dispose of excess glucose,” said Joseph Larner, MD, PhD, professor emeritus at UVa.

Larner and his colleagues isolated INS2 from cow livers, determined its chemical structure, synthesized it, then injected the compound into diabetic rats, with blood sugar levels at or above 500 milligrams per deciliter. The rats were then injected with insulin. Diabetes researchers at UVa were pleased that the more compound they injected, the more blood sugar decreased in the animals. “This compound is dose dependent and active. It potentiates the action of insulin,” explained David Brautigan, PhD, director of the Center for Cell Signaling at UVa.

Using computer modeling, Larner and Brautigan docked the INS2 compound onto an enzyme in cells called PP2C. If INS2 could activate PP2C, it would trigger other events in cells activated by insulin.

“INS2 was added and the purified PP2C enzyme was activated,” Brautigan said. “When we changed one amino acid in PP2C that the modeling predicted was the site for INS2, then the activation by INS2 was absent. In that way the enzyme assay confirmed the model.” The UVa group has been working to define the action of INS2 in hopes that it will potentially help millions of diabetics worldwide.; Source: University of Virginia Health System