Director of the Hormone Assay & Analytical Services Core

Drug Action
One of the most sought after advances in the treatment of diabetes is to non-invasively measure blood glucose. The goals of our studies are to optimize a method, which uses near infrared light to allow glucose measurement without the need to sample blood.
Treatment of type 1 diabetes requires the delivery of insulin through injections or pumps. Regardless of which approach is used, it results in an overinsulinization of muscle or underinsulinization of the liver. This in turn overrules a metabolic cost. We are working with pharmaceutical companies to develop and test insulin analogues, which can be administered by mouth or inhalation. In addition, we are testing insulin vesicles that can be targeted to the liver.
GLP-1 is a peptide released from the gut which stimulates and inhibits glucagon release. It may also have direct metabolic effects on muscle. In view of its therapeutic potential we are investigating its metabolic actions in vivo.

 The Portal Signal
Glucose distribution to muscle and liver following feeding is controlled by hormonal, substrate, and neural factors. Of particular importance are the plasma insulin and glucose levels and an unknown signal arising from the brain as a result of a comparison of the arterial system and the portal vein. Little is known about the nature of this signal (its origin, it mechanism of action). Likewise, it is not clear whether other metabolic substrate (i.e. free fatty acids, amino acids) can modify the effect on the liver. We are currently exploring these interactions.

Metabolic Action of Hormones
The plasma glucose level is precisely controlled by the balance between glucose production and glucose utilization. In turn each of these two rates are regulated by potent glucoregulatory feedback loops. The plasma glucose level can be sensed by the hepatocyte directly, by pancreatic a and b cells, and by neural sensors in the portal vein and hypothalamus. Hormonal and neural mediators are released in response to these sensors and they interact to control glucose uptake by muscle and fat and glucose production by the liver. We have studied the effects of the agonists and antagonists shown above on liver glucose production. We are now investigating these effects further and we are beginning to evaluate the interaction of these mediators in controlling liver glucose output.

More