Central Mechanisms That Regulate Glucose Metabolism in Humans

National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Type 2 diabetes is a chronic condition that affects the ability of the body to regulate glucose (sugar). When glucose levels are low, the liver can make glucose to increase levels in the body. This important process is called endogenous glucose production (EGP). Previous studies suggest that the central nervous system (CNS), including the brain, helps to coordinate this process by communicating with the liver through potassium channels. Control of EGP can be impaired in people with type 2 diabetes, which may contribute to the high levels of glucose seen in these individuals. The purpose of this study is to understand how activating these potassium channels in the control centers of the brain with a medication called diazoxide might inhibit the amount of glucose made by the liver. This is particularly important for people with diabetes who have very high production of glucose, which in turn causes hyperglycemia (high levels of sugar in the blood) that leads to diabetes complications.

In this study, the investigators will study healthy participants through a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Endogenous glucose production (the production of sugar by the liver) will be measured in patients given diazoxide (a medication that activates potassium channels in the brain that may affect glucose production in the liver through brain-liver signaling), compared with when a placebo is given.

EGP (a measure of the body's production of sugar) will be measured using analysis of blood samples taken throughout the pancreatic clamp procedure under various treatment conditions (eg, diazoxide or placebo) by monitoring changes in the level of a non-radioactive, naturally occurring form of glucose (sugar).

Inclusion Criteria: Healthy volunteers Exclusion Criteria: Hyperlipidemia Hypertension Heart disease Cerebrovascular disease Seizures Bleeding disorders Muscle disease