Preclinical studies have demonstrated in mouse models that (PYR1)-apelin-13 exerts a glucose-regulating action in vivo. The (PYR1)-apelin-13 effect on insulin sensitivity in healthy overweighed volunteers has been previously assessed in a phase I clinical trial (APELINS study; NCT02033473). The APELINS-2 clinical trial aims to expand the initial proof of concept to the population targeted by future innovative insulin-sensitizing therapies: patients living with type 2 diabetes.

Insulin sensitivity is measured using the hyperinsulinemic euglycemic glucose clamp method. The hypothesis of the investigators is that a continuous (pyr1)-apelin-13 infusion improves insulin sensitivity of type 2 diabetic patients compared to placebo infusion.

This study could bring new elements for understanding the pathophysiology of insulin resistance and type 2 diabetes mellitus in humans and could lead to the development of innovative therapies in type 2 diabetes mellitus.

Inclusion Criteria:

• Clinical diagnosis of type2 diabetes
• Body Mass Index between 27 and 33 kg / cm ²
• HbA1c < 8.5%
• Non-pathological Electrocardiogram
• Heart rate between 50 and 80 beats per minute at rest.
• Complete Blood Count (CBC) with no significant anomaly in terms of the investigator..
• Serum electrolytes without clinically significant abnormalities in terms of the investigator.
• Liver function tests without clinically significant abnormalities in terms of the investigator
• Renal function tests without clinically significant abnormalities in terms of the investigator
• Good peripheral vein (forearm and back of the hand).
• Agreement to participate in the establishment of a serum bank.
• Ability to sign informed consent.
• Affiliation to a social security scheme

Exclusion Criteria:

• Secondary prevention of cardio-vascular disease
• Insulin therapy or Glucagon Like Peptid 1 (GLP-1) analogs therapy in the 6 months before inclusion.
• Risk factor, treatment or electrocardiogram as recommended by International Conference on Harmonization (ICH) E14 "Clinical Evaluation of QT / QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs"
• Repeated a QTc interval> 450 ms measurement
• Risk factor for torsade de pointes: myocardial infarction, hypokalemia, family history of long QT syndrome
• Personal history of cancer.
• Positive HIV serology.
• Hepatitis B serology positive.
• Positive hepatitis C serology.
• Cognitive impairment or mental illness (at the discretion of the investigator).
• Chronic excessive alcohol consumption (consumption > 30g/day or 210g/week).
• Person under judicial protection, guardianship.
• Subject with a resting systolic blood pressure greater than 140 mm Hg and diastolic blood pressure greater than 90 mmHg
• Smoking more than 10 cigaret per day and can not be interrupted for 24 hours.