Although diabetes is known as a disease of uncontrolled blood glucose, medical research has also begun to focus on it as a blood vessel condition.
Currently, research is under way to study the relation of PKC-beta inhibitors to diabetic retinopathy.
In analyzing exactly how high blood glucose leads to kidney disease, neuropathy or retinopathy, researchers are examining the changes that uncontrolled glucose levels can cause in the small blood vessels in the kidneys, the nerves and the eyes.
Recent and very promising research is providing some answers about how prolonged high blood glucose causes diabetes-related complications, and it has identified one of the villains in this process.
Enzymes are proteins made by the body that bring about chemical reactions. We now know that the enzyme PKC-beta (protein kinase C-beta) acts to increase the formation of new blood vessels. When such formation is unwarranted and inappropriate, it can lead to trouble.
Why Is PKC-Beta So Important to People With Diabetes?
Scientists have found several forms of this enzyme, all apparently essential for sustaining life. Some forms are found more frequently in certain areas of the body.
PKC-beta is produced in excess during periods of high blood glucose. In other words, when there is too much blood glucose, this enzyme is turned on “too high.” When PKC-beta is turned on “too high,” it leads to the complications related to diabetes—primarily retinopathy, kidney disease and neuropathy, which are all related to small blood vessel damage—and possibly to larger blood vessel damage that can affect the heart.
Exploring the mechanisms that are involved in turning on PKC-beta beyond its normal levels is proving to be an exciting area for new diabetes research.
How Does High Blood Glucose Lead to Damage?
In addition to high levels of PKC-beta, a potent hormone growth factor known as vascular endothelial growth factor (VEGF) can be released into the bloodstream as a result of other complications related to diabetes. Combined, PKC-beta and VEGF have the added effect of causing new blood vessel growth and leakage.
The best example of how this can create problems is seen in the eye. When the eye is exposed to prolonged high blood glucose, it results in PKC-beta causing new blood vessel formation and/or leakage. The leaking blood vessels lead to a condition known as macular edema. This causes the retina to swell, leading to blurred vision and blind spots; if left untreated, it can even cause retinal detachment or blindness. Worse, the newly formed blood vessels can easily burst, flooding the eye with blood, which can also lead to total or partial blindness.
Exciting New Developments
One of the most exciting possibilities in the efforts to fight diabetes complications is the development of a PKC-beta inhibitor.
Eli Lilly and Company has developed LY333531, a PKC-beta inhibitor that stops the overgrowth of new blood vessels and the progression of the vessel leakage. This new drug (whose designated generic name is ruboxistaurin), which may be available in a couple of years, might eliminate the negative effect high blood glucose levels have on the eyes and kidneys.
Currently, research is under way to study the relation of PKC-beta inhibitors to diabetic retinopathy. Theoretically, a PKC-beta inhibitor has great potential to benefit patients with diabetes. Halting the progression of retinopathy and kidney disease in the diabetes population could bring in a new era of treatment.
Roger Corder, professor of experimental therapeutics at the William Harvey Research Institute and the Barts and London School of Medicine, wrote a commentary in the September 2002 issue of Clinical Science discussing the potential future role of PKC-beta inhibitors in the treatment of diabetes-related complications.
Corder states that based on animal studies—primarily with rats—LY333531 inhibits PKC-beta formation. In rat studies, this compound has normalized retinal and kidney vascular function, though not completely to the level of kidney function found in nondiabetic rats.
More recent studies also show improvement of impaired nerve function in diabetic rats. Corder therefore speculates that PKC-beta inhibitors will play a role in the treatment of diabetes-related microvascular complications such as eye disease, kidney disease and nerve damage.
He notes that phase 2 and 3 clinical trials, involving humans, are currently being conducted and adds that this novel drug may also have a role in treating macrovascular disease involving the heart and large blood vessels, although this remains to be proven in studies.
Tight Control Still the Best Weapon
Despite the potential held out by this new research, the greatest weapon people with diabetes have is tight control of blood glucose. Near-normalization of blood-glucose levels remains the primary goal of diabetes treatment and care.
Go back to Home Page
Go back to Diabetes Directory