George L. King, MD is the Director of Research, Senior Vice President, and Head of the Section on Vascular Cell Biology at Joslin Diabetes Center, as well as a Professor of Medicine and Ophthalmology at Harvard Medical School. He received his medical degree from Duke Medical School, completed medical residency training at the University of Washington Affiliated Hospitals in Seattle, and then completed training in Endocrinology and Diabetes as both a Research Associate and a Clinical Associate at the National Institutes of Health. He has been at Joslin and Harvard Medical School since 1981.
Dr. King has received numerous awards, including the Cogan Award from the Association for Research and Vision and Ophthalmology, the Edwin Bierman Award from American Diabetes Association, the Alcon Award for Vision Research, and the Annual Award for Excellence in Research from the Japan Society of Diabetic Complications. He also was named Honorary Professor at the Fu Dan Institute of Endocrinology and Diabetology at Fu Dan University, Shanghai, China, and received JDRF Mary Tyler Moore/S. Robert Levine Award for Clinical Research from Juvenile Diabetes Research Foundation. Recently, Dr. King was among a group of scientists who received the Champalimaud Award, the most prestigious award for vision research in the world.
Dr. King’s research focuses on the complications of diabetes which is the main cause of suffering in people with diabetes. The most serious complications involve the eye, kidney, heart, large arteries, brain, and nerves. The laboratory of Dr. King studies the molecular mechanisms by which hyperglycemia and insulin resistance may lead to these complications in people with diabetes and insulin resistance.
Dr. King’s laboratory has shown that activation of protein kinase (PKC) is a major signaling pathway by which hyperglycemia causes pathologies in the retina, kidney, cardiovascular systems, and wound healing. One major discovery made in Dr. King’s laboratory has been the identification of vascular endothelial growth factors (VEGF) as a main cause of the severe form of diabetic retinopathy or eye disease. This finding has led to the development of the use of inhibitors of VEGF as a treatment for severe form of diabetic eye disease which now has been approved by FDA and is a main treatment to prevent vision loss in diabetes.
Dr. King is also the founder of the Medalist Study which includes over 1,000 people with insulin dependent diabetes who have lived for more than 50-85 years. Dr. King conceived the Medalist Study in order to discover new protective factors that could prevent the development of diabetic eyes, kidney, nerves, and neurological disease in all people with diabetes. This new concept has been confirmed by the findings of protective factors in the eye and kidney in Dr. King’s laboratory and other laboratories around the world. The Medalist study has also provided exciting news regarding the possibility that people with type 1 diabetes have functional residual beta cells functions. This idea of people with type 1 diabetes retaining beta cells has supported strongly that beta cell regeneration is a possible treatment in people with type 1 diabetes.
The third area of study concerns insulin’s role in regulating cardiovascular function in physiological and pathophysiological states. Insulin resistance is an important risk factor for cardiovascular diseases not only in people with diabetes, but also in those who have high blood pressure, lipid abnormalities, obesity, or hypertension. Dr. King’s laboratory has shown that the loss of a specific part of insulin’s action in blood vessels involving functions such as vasodilation, anti-oxidative stress, and expression of atherosclerosis factors could be important for development of cardiovascular diseases. Dr. King’s laboratory has identified the concept that only part of insulin’s action in the vascular wall are lost which coordinating the term of selective insulin resistance which can exaggerate for atherosclerosis or poor angiogenesis which are hall marks of diabetic cardiovascular diseases, wound healing, and neuropathy. These studies have shown insulin-resistant or diabetic state causes a selective loss of insulin’s action with regard to one specific signaling pathway—IRS–PI 3-kinase–Akt—which mediates many of insulin’s anti-atherogenic actions, such as production of nitric oxide (NO) to dilate blood vessels and the expression of VEGF to improve heart perfusion, decrease of endogenous proteins such as VCAM-1 in order to decease inflammation in the large blood vessels, and thus decrease the rate of atherosclerosis or other pathologies. One potential treatment for people with diabetes and cardiovascular diseases is to improve insulin’s action, especially through the IRS-Akt pathway which can potentially decrease cardiovascular complications in people with diabetes.
Dr. King is also the Director of Joslin’s Diabetes Research Center designated by NIH-NIDDK which is a very important and prestigious grant that is awarded to only a few centers in the USA and encourages different investigators to work together.
Dr. King’s laboratory proposed that activation of protein kinase C—especially the beta (PKC-beta) and delta (PKC-delta) isoforms—is the major signaling pathway by which hyperglycemia causes pathologies in the retina, kidney and cardiovascular systems. In a series of studies using cultured vascular cells from the retina, renal glomeruli and arteries, Dr. King’s laboratory demonstrated that hyperglycemia can activate PKC to induce vascular pathologies. Dr. King’s laboratory also characterized an isoform-selective inhibitor to PKC-beta, which, in diabetic animal models, prevents and stops the early changes of diabetic retinopathy, nephropathy and cardiovascular dysfunction.
Currently Dr. King’s laboratory is exploring the targets of PKC-beta and delta isoform activation in various vascular tissues, including retinal vascular cells, cardiomyocytes, arterial vascular cells, renal mesangial cells and podocytes. These targets involve extracellular matrix proteins, enzymes such as eNOS, and NADPH oxidase, cytokines and growth factors such as VEGF, TGF-beta, CTGF and endothelin, as well as transcription factors. Recently, Dr. King’s laboratory has reported that PKC delta activation by hyperglycemia can activate two independent signaling cascades, one NF-κB and the other is a tyrosine phosphatase (SHP-1) to reduce apoptosis of retinal and renal cells important in the initiation of diabetic retinopathy and nephropathy.
The second area of study concerns insulin’s role in regulating cardiovascular function in physiological and pathophysiological states. Insulin resistance is an important risk factor for cardiovascular diseases not only in people with diabetes, but also in those who have high blood pressure or lipid abnormalities or are obese.
Dr. King’s laboratory has shown that at the molecular and biochemical levels, insulin can regulate many vascular and cellular functions, including the enzyme activities of eNOS and HO-1, the expression of cytokines such as VEGF and endothelin and the migration and growth of smooth muscle cells. His laboratory postulated that insulin in the normal state can have anti-atherogenic actions. However, the loss of insulin’s normal action, in combination with the elevation of insulin levels found in insulin-resistant states, can lead to pro-atherogenic conditions in large blood vessels. These studies show an insulin-resistant or diabetic state causes a selective loss of insulin’s action with regard to one specific signaling pathway—IRS–PI 3-kinase–Akt—which mediates many of insulin’s anti-atherogenic actions, such as production of nitric oxide (NO) to dilate blood vessels and the expression of VEGF to improve heart perfusion and HO-1 for endogenous anti-oxidative stress actions.
Clinically, Dr. King is leading a comprehensive study to identify protective factors in a large group of Type 1 diabetic patients with diabetes duration over 50 years, called the Medalist Study. Over 40% of the Medalist diabetic patients do not have significant complications, even after 50-85 years of diabetes. Studies using molecular, genetic, biological and physiological methods are ongoing to identify these protective factors against the adverse effects of hyperglycemia of diabetes
Johns Hopkins University
Duke Medical School
University of Washington Affiliated Hospitals
University of Washington Affiliated Hospitals
Duke University and National Institutes of Health, National Institutes of Arthritis, Diabetes, Digestive and Kidney Diseases, Bethesda, MD
Internal Medicine, Endocrine & Metabolism
- Cardiovascular Disease
Dr. King has received numerous awards, including the Cogan Award from the Association for Research and Vision and Ophthalmology, the Stadie Memorial Award and Lectureship from the Philadelphia Affiliate of the American Diabetes Association, the Alcon Award for Vision Research and the Annual Award for Excellence in Research from the Japan Society of Diabetic Complications.
Dr. King also was named Honorary Professor and Director of the Fu Dan Institute of Endocrinology and Diabetology at Fu Dan University, Shanghai, China.
Recently, Dr. King was among a group of scientists who received the Champalimaud Award, the most prestigious award for vision research.