IRAPs (Secreted Insulin Regulated AminoPeptidase): a New Insulin Sensitivity Biomarker

Study Overview
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Brief Summary
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Previous studies have demonstrated defects in the trafficking and translocation of GLUT4 glucose transporter in skeletal muscle and adipose tissue to be a major cause of insulin resistance in humans. IRAP (Secreted Insulin Regulated AminoPeptidase) is a protein which collocalizes and is translocated with GLUT4 to the plasma membrane in response to insulin. The extracellular domain of IRAP is cleaved and released in the bloodstream. Therefore, IRAP plasma concentration could be a good marker of insulin sensitivity. In this study the investigators seek to confirm this hypothesis by using the gold standard of insulin sensitivity assessment: the hyperinsulinemic-euglycemic clamp. It is a multicenter descriptive study.

Official Title
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Evaluation of Plasma IRAP Secreted Protein as a New Insulin Sensitivity Biomarker, Using Hyperinsulinemic Euglycemic Clamp

Conditions
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Insulin Resistance

Intervention / Treatment
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* Other: It is a hyperinsulinemic-euglycemic clamp.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women (sex ratio = 1) Aged from 18 to 35 years Fasting glycemia < 6mmol/L Total cholesterol < 7mmol/L Triglycerides < 1.5 mmol/L CRPus < 5 mg/L Creatinine clearance < 80mL/min according to Cockroft formula Liver enzymes (ALanine AminoTransférase and ASpartate AminoTransférase) < 1.5 times normal values Exclusion Criteria: Subject not in compliance with the recommendations of French National Law in force Medical history of metabolic disease (diabetes, dyslipidemia), endocrine disease, renal insufficiency Drug use that could affect glucose metabolism and the renin angiotensin aldosterone system Blood pressure > 140/90mmHg Tea and coffee consumption more than 5 cups per day Subject who smoke more than 5 cigarettes per day

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Other: It is a hyperinsulinemic-euglycemic clamp.<br>* The hyperinsulinemic-euglycemic clamp includes three periods: A basal period (from T-30 to T0) The infusion of insulin at a constant rate (first level at 1 mUI.kg-1.min-1 and a second level at 2 mUI.kg-1.min-1) during 4 hours ( to obtain stable hyperinsulinemia) The infusion of glucose at variable rate (so as to maintain euglycemia)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IRAP plasma concentration during the hyperinsulinemic euglycemic clamp | Enzyme-linked Immunosorbsent assay (Sandwich ELISA) | 30 min before the clamp and during the clamp every 10 min for a duration of 240 min. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Infusion Rate (GIR) | It is an average rate of glucose infused at steady state of the first and second level of insulinemia infusion | at T90, T100, T110, T120 minutes and T210, T220, T230, T 240 minutes | 
| Oxydative stress markers | TBARS, GSH, GSSG and nitroalbumin assessments | at T0, T120 and T240 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IRAP, insulin sensitivity marker