Neural Mechanism of Aldosterone-induced Insulin Resistance

Summary

Patients with high aldosterone hormone have higher blood glucose than normal people. This study is being done to understand how aldosterone hormone affects the nerve activity that controls blood flow in the muscles and blood glucose. The information may be helpful in selecting blood pressure medications which can improve not only blood pressure but also improve blood sugar.

Conditions

• Hypertension

Interventions

DRUG

DEFINITY® infusion

The DEFINITY® vial contains components that upon activation yield perflutren lipid microspheres, a diagnostic drug that is intended to be used for contrast enhancement during echocardiographic procedures. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic liquid, which upon activation with agitation, provides a homogeneous, opaque, milky white injectable suspension of perflutren lipid microspheres. The suspension of activated DEFINITY® will be infused intravenously at a rate of 0.20 to 0.27 ml/min, not to exceed a maximum dose of 2 vials per study subject per day or visit.

DRUG

Human Recombinant Regular Insulin infusion

The plasma insulin concentration will be acutely raised and maintained at at a steady state by a prime-continuous insulin infusion.

DRUG

Dextrose infusion

The plasma glucose concentration will be held constant at 90 mg/dl by a variable glucose infusion during euglycemic hyperinsulinemic clamp

PROCEDURE

Flow mediated vasodilation

Flow mediated vasodilation (FMD), which is a non-invasive assessment of endothelial function, will be performed on the brachial artery using ultrasound. After a clear picture of the artery has been obtained, the cuff on the same arm will be inflated until it is tight for five minutes. During and following this, the subject's arm will continue to be imaged to monitor maximal increase in the brachial artery diameter.

PROCEDURE

Endothelial cell collection

We will collect endothelial cells from a superficial vein, usually in the arm. Following insertion of a peripheral intravenous (IV) catheter, we will collect cells from the inner lining of the vein using a thin, flexible J-tipped wire. The wire will be inserted through the IV into the vein and then removed, along with a sampling of endothelial cells. The cells collected will be processed and stained for several proteins involved in endothelial cell function, using immunofluorescent technique.

PROCEDURE

Microvascular perfusion assessment using Definity

Using high-resolution ultrasound, we will measure skeletal muscle blood flow during infusion of a solution containing the octafluoropropane microbubble contrast agent, Definity. The solution will be a dilution of 1 vial of Definity to 30 cc of normal saline. The ultrasound probe will be placed over the forearm to obtain images while octafluoropropane microbubbles (Definity) are infused intravenously at the rate of 0.20 to 0.27 ml/min, not to exceed a maximum dose of 2 vials per study subject per day or visit. The microvascular perfusion assessment using Definity be performed at rest as well as during slow and fast handgrip exercises.

PROCEDURE

Microneurography

Sympathetic nerve activity from the peroneal nerve measured by inserting a tiny needle directly into the nerve in the leg. Investigators will localize the nerve by electrical stimulation over the skin using a blunt probe. .The recording needle will remain in position throughout the study.

Sponsors & Collaborators

• Wanpen Vongpatanasin

  lead OTHER

Principal Investigators

• Wanpen Vongpatanasin, MD · UT Southwestern Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2010-11-30

Primary Completion

2025-12-31

Completion

2025-12-31

Countries

• United States

Study Locations