Regulation of Carbohydrate Metabolism in Humans

At any given time, the rate of change in plasma glucose concentration is determined by the balance between the amount of glucose entering the blood stream and the amount of glucose leaving the blood stream. The former is derived from food or from the liver, whereas the later is determined by the rate of uptake of glucose by insulin-dependent and -independent tissues. This balance is disrupted in people with diabetes due to alterations in insulin secretion, insulin action, and glucose effectiveness (defined as the ability of glucose to stimulate its own uptake and to suppress its own release). We are seeking to gain a greater understanding of how these abnormalities alone and in combination cause hyperglycemia in people with diabetes mellitus.

To address this question, our laboratory makes extensive use of isotopic dilution (stable and radioactive) techniques, indirect calorimetry, organ catheterization (hepatic, leg, forearm), and mathematical models. We are particularly interested in the effects of obesity, diabetes, and various treatment modalities on the regulation of hepatic glycogenolysis, gluconeogenesis, and glycogen synthesis in humans. We use glucose and insulin clamps as well computer-generated insulin and glucose infusion algorithms to assess the impact of physiologic changes in glucose, insulin, glucagon, cortisol, incretins, and various substrates (e.g., free fatty acids) on carbohydrate, fat, and protein metabolism in diabetic and nondiabetic humans. We also are examining the impact of different routes of insulin (portal versus peripheral) and glucose (enteral versus intravenous) delivery on glucose tolerance. Our long-term goal is to develop rational and effective therapies for the treatment and prevention of diabetes mellitus and its associated complications.