PKC Research at Joslin Diabetes Center - 1981 - 2005
A summary of more than 20 years of study dedicated to understanding the molecular mechanisms by which hyperglycemia damages vascular tissues, and testing PKC inhibitors to prevent the long-term complications of diabetes.
One of the most difficult tasks for diabetes patients is controlling the level of glucose in their blood. As clinical studies have shown, abnormally high glucose, or hyperglycemia, over time causes a host of serious health problems, including diseases of the kidney, retina, nerves and heart. All long-term diabetic complications - which affect people with both type 1 and type 2 diabetes - begin with damage to blood vessels.
Since the early 1980s, George L. King, M.D., Director of Research and Head of the Section on Vascular Cell Biology at Joslin Diabetes Center, has studied the role of PKC in the development of vascular (blood vessel) dysfunction. One of his lab’s most significant efforts over the past two decades has been to understand the molecular mechanisms by which hyperglycemia damages small blood vessels and to find drug targets to prevent or delay the progression of diabetic vascular diseases.
Joslin’s major contributions to PKC research include:
- Making the original observation that PKC is activated by hyperglycemia
- Identifying the first isoform, PKC-beta
- Publishing the first studies showing that a PKC inhibitor can prevent diabetes-induced vascular dysfunction
- Providing the first evidence that vascular endothelial growth factor (VEGF) increases PKC in vivo, leading to blood vessel abnormalities, which improved after treatment with the PKC inhibitor
- Demonstrating for the first time that PKC-beta is persistently activated in the large blood vessel tissues of the heart and aorta
- Publishing the first evidence that PKC is involved in adhesion of white cells to blood vessel walls, and that treatment with the PKC inhibitor prevented adhesion and decreased oxidative stress
This paper examines these and other milestones of PKC research at Joslin over the past 20 years, and briefly explains how diabetes affects the kidney and retina.
Please click on the link below for the complete paper(Requires Acrobat Reader).