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Regulation of Endogenous Glucose Production

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Regulation of Endogenous Glucose Production by Central KATP Channels

Type 2 diabetes 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.

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Drug - Diazoxide

Non-diabetic participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) before undergoing the pancreatic clamp study. T2D participants will have their blood sugar levels normalized, and will then receive diazoxide at a dose of 4-7 mg/kg (based upon weight) before undergoing the pancreatic clamp study.

Drug - Nicotinic acid

T2D participants will have their blood sugar levels normalized and will additionally receive nicotinic acid infusion based on weight (0.01 mg/kg/min) to lower free fatty acid levels before undergoing the pancreatic clamp study.

Drug - Placebo

Non-diabetic participants will receive placebo and undergo the pancreatic clamp study. T2D participants will be admitted the evening before the study day to normalize blood sugar levels to that of a healthy person. They will then receive placebo the next morning and undergo the pancreatic clamp study.

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Regulation of Endogenous Glucose Production by Central KATP Channels

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NCT03540758

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