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

Hospices Civils de Lyon21 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Insulin Resistance

Interventions

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)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

IRAP plasma concentration during the hyperinsulinemic euglycemic clamp

Enzyme-linked Immunosorbsent assay (Sandwich ELISA)

Time frame: 30 min before the clamp and during the clamp every 10 min for a duration of 240 min.

Secondary Outcomes

Glucose Infusion Rate (GIR)

It is an average rate of glucose infused at steady state of the first and second level of insulinemia infusion

Time frame: at T90, T100, T110, T120 minutes and T210, T220, T230, T 240 minutes

Oxydative stress markers

TBARS, GSH, GSSG and nitroalbumin assessments

Time frame: at T0, T120 and T240 min