Regulation of Endogenous Glucose Production by Central KATP Channels
Albert Einstein College of Medicine
Summary
Type 2 diabetes (T2D) affects the ability of the body to process glucose (sugar). Under fasting conditions, the liver is able to make sugar to maintain glucose levels in an important process called endogenous glucose production (EGP). Previous studies suggest that the central nervous system (CNS), including the brain, helps to regulate levels of glucose in the body by communicating with the liver. This process can be impaired in people with type 2 diabetes, and can contribute to the high level of glucose seen in these individuals. The purpose of this study is to understand how activating control centers of the brain with a medication called diazoxide can affect how much glucose (sugar) is made by the liver. This is particularly important for people with diabetes who have very high production of glucose, which in turn can lead to diabetes complications.
Description
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 (a measure of the body's production of sugar) will be measured…
Eligibility
- Age range
- 21–70 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: For healthy (non-diabetic) participants: * Age: 21-70 years old * Body Mass Index (BMI) under 40 kg/m\^2 * Negative drug screen (see below) * Normal Hemoglobin A1c (HbA1c) and fasting glucose * In general good health (see below for exclusions) * Not participating in any other research study besides those done by the study team For T2D participants: * Age: 21-70 years old * BMI under 40 kg/m\^2 * Stable and moderate-to-poor glycemic control (HbA1c: 8.0-12.0%) * Negative drug screen (see below) * Not suffering from a previously diagnosed proliferative retinopathy, signifi…
Interventions
- DrugDiazoxide
Non-diabetic participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) during the pancreatic clamp study.
- DrugNicotinic acid
Non-diabetic participants will receive nicotinic acid infusion based on weight (0.01 mg/kg/min) during the pancreatic clamp study.
- DrugPlacebo
Non-diabetic participants will receive placebo and undergo the pancreatic clamp study. T2D participants will have their blood sugar levels normalized, and will then receive a taste-matched placebo for diazoxide before undergoing the pancreatic clamp study.
Location
- Albert Einstein College of MedicineThe Bronx, New York