The overall purpose of this study is to learn more about the metabolic effects of angiotensin-(1-7) in the insulin resistant state associated with obesity. Pharmacologic approaches to increase angiotensin-(1-7) levels or its actions are currently in development for treatment of metabolic-related diseases such as obesity and type II diabetes, based on findings from animal studies. It is unclear if this peptide contributes to the regulation of metabolism in humans. The investigators will test if angiotensin-(1-7) infusion can improve insulin sensitivity measured by hyperinsulinemic-euglycemic clamp methods in individuals with obesity and insulin resistance. The investigators will also examine for changes in blood pressure and related hemodynamic and hormonal changes following angiotensin-(1-7) infusion.
This is an outpatient study that requires a screening visit and two study days in the Vanderbilt Clinical Research Center. Subjects will be asked to stop taking any medications for high blood pressure for at least 2 weeks prior to the study. Subjects will receive intravenous angiotensin-(1-7) or saline infusion on two separate study days, with each study day lasting approximately four hours. There will be at least one week of washout between study days. On each study day, subjects will be instrumented with two intravenous catheters (one for blood sampling and one for drug infusion), arm and finger blood pressure cuffs, and sticky patches to measure heart rate throughout the study. The investigators will take baseline measurements of blood pressure and heart rate and collect blood samples. The investigators will also perform a rebreathing test to measure the heart's pumping capacity. After baseline measurements, the investigators will infuse angiotensin-(1-7) or saline for 30 minutes, with blood pressure and heart rate measured every 10 minutes. At the end of 30 minutes, blood samples will be collected and the rebreathing test will be repeated. The investigators will continue the angiotensin-(1-7) or saline infusion for an additional 2 hours while performing a hyperinsulinemic-euglycemic clamp to measure insulin sensitivity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
26
This is a biologically active endogenous angiotensin peptide. It may play an important role in the regulation of blood pressure by dilating blood vessels as well as a role in the regulation of insulin action.
Normal saline will be used as a placebo comparator.
Vanderbilt University Medical Center
Nashville, Tennessee, United States
RECRUITINGWhole-Body Insulin Sensitivity
Whole-body insulin sensitivity will be defined as the glucose infusion rate needed to maintain euglycemia during steady state (time=90 to 120 minutes) of the hyperinsulinemic-euglycemic clamp following angiotensin-(1-7) versus saline infusion. The insulin sensitivity will be corrected by body weight, lean body mass, and steady-state plasma insulin concentrations.
Time frame: steady-state (time 90 to 120 minutes) during hyperinsulinemic-euglycemic clamp
Blood Pressure
The change in blood pressure following angiotensin-(1-7) versus saline infusion.
Time frame: 150 minutes
Heart Rate
The change in heart rate following angiotensin-(1-7) versus saline infusion.
Time frame: 150 minutes
Cardiac Output
The change in cardiac output following angiotensin-(1-7) versus saline infusion.
Time frame: 150 minutes
Stroke Volume
The change in stroke volume following angiotensin-(1-7) versus saline infusion.
Time frame: 150 minutes
Systemic Vascular Resistance
The change in systemic vascular resistance following angiotensin-(1-7) versus saline infusion.
Time frame: 150 minutes
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