Serendipitous findings by scientists in Belgium, France, and Canada point to a new potential therapeutic target for type 2 diabetes: a gene called SHIP2 that appears to act as a brake on insulin production. The report appears in the January 4 issue of Nature.
The investigators found that genetically engineered newborn mice that lacked copies of the SHIP2 gene showed signs of hypoglycemia—they were blue or pale, lethargic, showed signs of respiratory distress, and failed to gain weight—and died within 3 days of birth. Further study revealed that the mice were hypoglycemic because of hypersensitivity to insulin rather than overproduction of the hormone.
Mice with one normal copy of SHIP2 also appeared to be more sensitive to insulin than mice with both copies of the gene. Because SHIP2 appears to control sensitivity to insulin, it is possible that mutations in the gene may play a role in the insulin resistance seen in diabetes. The search for SHIP2 mutations in humans is under way.
The work "identifies SHIP2 as a critical and essential negative regulator of insulin signalling and insulin sensitivity in vivo," the researchers noted. "Thus, SHIP2 is a potential therapeutic target for the treatment of type 2 diabetes, and a candidate gene that predisposes to the same disease."
