New research from
the University of Cincinnati (UC) points to the naturally produced protein
apolipoprotein A-IV (apoA-IV) as a potential target for a new diabetes
therapeutic.
Patrick Tso, PhD, professor in the UC Department
of Pathology and
Laboratory Medicine, has published research on the ability of apoA-IV to
reduce blood
sugar levels and enhance insulin secretion.
The results appear the week of May 21, 2012, in the
online early edition ofProceedings
of the National Academy of Sciences.
ApoA-IV is secreted by the small intestine in
response to fat absorption.
Previous studies have shown apoA-IV to be elevated in humans following gastric
bypass—coinciding with improvement in symptoms for diabetes.
The Tso team found that mice deficient in apoA-IV
had impaired glucose tolerance (insulin was not secreted to move glucose from
the blood stream). These mice also developed diabetes when continuously fed a
high-fat diet. When injected with apoA-IV, these same mice showed improved
insulin response to glucose, despite a diet high in fat.
Tso's team also tested the response to injected
apoA-IV in diabetic mice and found it reduced glucose levels among that group
as well.
Tso says their research shows apoA-IV to behave
similar to an incretin—a gastrointestinal hormone causing an increased release
of insulin after eating to combat the onset of elevated blood glucose. Two
well-known incretins that have been used in the development of existing
diabetes medications include gastric inhibitory peptide (GIP) and glucagon-like
peptide-1 (GLP-1).
"The problem with both of these incretins is
that they are short-lived—lasting only for minutes—and are quickly inactivated
by an enzyme," says Tso. "They have also been linked to hypoglycemia,
or low blood sugar, when administered when the body has a low glucose
concentration. The challenge is to find something safer with a longer
half-life."
Tso says apoA-IV has a long half-life (between
seven and eight hours) and that tests in his lab showed it to have no effect on
glucose levels when administered at low glucose concentrations. Instead, he
says, it seems to function to normalize glucose.
The University of Cincinnati has licensed this
research finding to a startup biotech company, Apofore Corporation, formed by
HealthCare Ventures of Cambridge, Mass. Apofore will further study apoA-IV in
humans in an effort to develop a novel diabetes therapeutic.
Journal reference: Proceedings
of the National Academy of Sciences
Provided by University
of Cincinnati Academic Health Center
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