New Target for Antidiabetic Agents
Identified
U.S. researchers identify a protein that could
serve as a new target for drugs designed to treat
type II diabetes.
The protein, known as TRB3, is actually a homolog
of a protein found in the fruit fly Drosophila
tribbles, senior author Dr. Marc Montminy, from
the Salk Institute for Biological Studies in La
Jolla, California, and colleagues note.
The focus on TRB3 was the result of a search to
identify proteins that modulate the activity of
Akt, a main target of insulin that blocks hepatic
glucose output when glucose is available from
food. Mice lacking the Akt gene demonstrate insulin
resistance similar to that seen in humans with
type II diabetes.
Dr. Montminy's team found that TRB3 acts as a
negative modulator of Akt and that its expression
is increased under fasting conditions. By binding
to Akt, TRB3 prevents the enzyme from being activated
by insulin, leading to increased glucose output
from the liver.
Elevated hepatic levels of TRB3 RNA and protein
were identified in diabetic mice compared with
wild-type mice, the authors report. Hepatic overexpression
of TRB3 was associated with hyperglycemia and
glucose intolerance.
Based on these findings, the researchers suggest
that TRB3 may be an "attractive drug target
in the treatment of type II diabetes." Science
2003;300:1574-1577.
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