The investigators will test the null hypothesis that there will be no changes in the insulin-mediated suppression of endogenous glucose production (EGP) in response to autonomic blockade. To test this hypothesis, the investigators propose to determine the role of the autonomic nervous system in hepatic insulin resistance.
In this study, the investigators will test the null hypothesis that there will be no changes in the insulin-mediated suppression of endogenous glucose production (EGP) in response to autonomic blockade. The investigators will measure EGP at baseline (EGPBsl) and during the last 30 minutes of a hyperinsulinemic euglycemic clamp (EGPClamp) on two different occasions (intact and Blocked study days). A double blinded randomize cross-over design will be used. Subjects will be randomized to either the intact or blocked days and a month later will be crossed-over to the other arm. The investigator performing the analysis will also be blinded to the treatments received. At baseline in both study days it is expected to see any differences since the same subject will serve as his own control. During the clamp, insulin suppresses EGP. In obese insulin resistant subjects this suppression should be blunted. If the hypothesis is correct, it is expected an improvement in the suppression by insulin of EGP during autonomic blockade only. For this study, the primary endpoint therefore, will be the EGP during the clamp between the intact and blocked days. H0= {(EGPClamp)Blocked - (EGPClamp)Intact}=0\]
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Trimethaphan 4 mg/min IV will be given as a pharmacological tool to study the role of the autonomic nervous system on the regulation of endogenous glucose production by the liver.
IV saline at a rate of 48 mL/hr, will be given during the insulin clamp to resemble the volume infused in the intact day
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Endogenous Glucose Production
Amount of label glucose appearance
Time frame: Duration of the study (4 hours)
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