Human Growth Hormone
Involved In Diabetic Kidney
Disease Say Study
Ohio University <>
Contact: Kelli Whitlock <>
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.
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.
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.
"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.
The findings were presented June 13 at the annual meeting of the Endocrine Society in San Diego.
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.
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.
Growth hormone antagonists inhibit the action of the hormone at the cellular level by binding to receptors usually claimed by growth hormone.
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.
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.
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."
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.
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.
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.
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.
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.