Presence of an activator of pyruvate dehydrogenase in human circulation: Elevation following a glucose load and possible relation to an insulin mediator

Our earlier observation that the chemical mediator of insulin action stimulates lipid synthesis in primary cultures of rat hepatocytes prompted us to examine its presence in human serum and its regulation by changes in insulin levels. Serum samples were obtained from normal subjects following an oral 100 gm glucose tolerance test (GTT; n=10). An acid soluble, heat stable and charcoal non-absorbable substance was extracted from different sera and tested for their ability to stimulate liver mitochondrial pyruvate dehydrogenase (PDH). This substance obtained from GTT samples at 1 1000 final dilution caused significantly higher stimulation of PDH when compared to that obtained from fasting samples. These results demonstrate the presence of an activator of PDH (molecular weight ∼ 1000–2000) in human circulation. Since the activator of PDH is modulated by physiological perturbation such as oral glucose ingestion, known to cause changes in circulating insulin levels, it may possibly be related to insulin mediator.