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- SAN DIEGO -- A new study of growth hormone suggests it plays
a role in the onset of Type I diabetes-induced kidney disease. Called diabetic
nephropathy, the disease affects 10 percent to 21 percent of all people
with diabetes.
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- Researchers at Ohio University induced
Type I diabetes in normal mice and in mice in which the growth hormone
receptor that binds the substance to cells had been genetically disrupted.
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- Ten weeks later, they examined the kidneys
of all the mice. While the normal mice had evidence of diabetic kidney
disease, the mice whose receptors had been disrupted did not.
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- "This clearly suggests growth hormone
is important in the development of Type I diabetes-induced kidney damage,"
said John Kopchick, Goll-Ohio Eminent Scholar and professor of molecular
biology at Ohio University.
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- The findings were presented June 13 at
the annual meeting of the Endocrine Society in San Diego.
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- Produced by the pituitary gland, growth
hormone promotes normal body growth and development by altering chemical
activity in cells. It stimulates the production of protein in muscle cells
and the release of energy from the breakdown of fats.
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- Kopchick led the team of researchers
working on this project, which is part of a larger study under way in the
university's Edison Biotechnology Institute that has resulted in the development
of growth hormone antagonists, the basis for a new class of drugs that
one day may be used to treat a variety of diseases, including acromegaly,
some forms of cancer and diabetic eye disease.
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- Growth hormone antagonists inhibit the
action of the hormone at the cellular level by binding to receptors usually
claimed by growth hormone.
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- Human and animal growth hormones contain
a chain of 191 amino acids. Kopchick's research team, which included co-inventor
Wen Chen, a former senior scientist with the institute now with Clemson
University, discovered that by replacing the amino acid glycine -- number
119 in the chain in animals and 120 in humans -- with almost any other
amino acid, the growth hormone turns from a growth hormone agonist, or
enhancer, to a growth hormone antagonist, or inhibitor.
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- Kopchick's research team conducted studies
in the mid-1990s on the effect of growth hormone antagonist on Type I diabetic
mice. Those studies, published previously in the journal Proceedings of
the National Academy of Sciences, found that mice genetically engineered
to express growth hormone antagonist did not develop diabetic kidney disease.
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- Researchers wanted to know if kidney
disease was prevented because of the inhibition of the growth hormone pathways
caused by the antagonist or if the antagonist prompted some other reaction
that led to disease prevention. "We don't know how growth hormone
is involved -- that's what we're looking at now," Kopchick said, "but
we know it is involved."
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- In addition to his studies of growth
hormone's involvement in diabetic kidney disease, Kopchick also has examined
the hormone's role in the onset of diabetes-induced eye disease. Results
of a collaborative study with Lois Smith at Harvard University announced
last year in the journal Science suggested the growth hormone antagonist
may prevent a destructive form of several eye diseases, including diabetic
retinopathy.
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- The university received U.S. patents
on growth hormone antagonist in 1994 and 1997. Four more patents are pending.
Sensus Drug Development Corp. in Austin, Texas, holds the license for the
invention and currently is using the technology to develop growth hormone
antagonists and related drugs for human diseases in which growth hormone
is elevated, or diseases in which growth hormone has been implicated.
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- Results from Sensus' Phase III clinical
trial of a growth hormone antagonist drug, pegvisomat, for use in the treatment
of acromegaly will be presented June 15 at the Endocrine Society meeting.
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- Kopchick's diabetic nephropathy studies
were supported in part by the Central Ohio Diabetes Association, Sensus
and the State of Ohio's Eminent Scholar Program. The original research
on growth hormone antagonist was supported in part by Ohio's Thomas Edison
Program.
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- Kopchick is a senior scientist with the
Edison Biotechnology Institute and holds a faculty appointment in the College
of Osteopathic Medicine. Study co-authors were Linda Bellush, a research
scientist, and Amy Holland, a research technician, both with the institute;
and Sophie Dublier, Liliane Striker and Gary Striker, with the University
of Miami.
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