Characterizing the Incretin Effect of Amino Acids and Defining GLP-1 Role on Skeletal Muscle — Incretin  

Sarcopenia Clinical Trial

Official title: Characterizing the Incretin Effect of Amino Acids (AA) and Defining the Effect of GLP-1 on Muscle Microvascular Blood Flow and Muscle Protein and Glucose Metabolism in Older Age.

Status Completed

Clinical Trial Summary

This study has two protocols the aims of which are:

1. To identify age-related effects of AA on incretin secretion and whether and to what extent AA exhibit a true incretin effect (gut- mediated increases in plasma insulin) in younger individuals. (Protocol 1)

2. To define the extra-pancreatic ''novel'', insulin independent effects of glucagon like peptide-1 (GLP-1) on postprandial muscle protein and glucose metabolism and microvascular blood flow. (Protocol 2)

Clinical Trial Description

Protocol 1:

This will explore the first aim. 8 Healthy younger volunteers will be recruited to under go 3 arms cross over studies. Interventions will include oral and intravenous amino acids, in addition to intravenous GLP-1 and glucose dependent insulinotropic polypeptide (GIP).

8 older subjects also will be recruited for comparison of the response of GI hormones to amino acids oral feed between young and older men.

Therefore the total number will be recruited to perform this protocol is 16.

Post intervention in all visits, measurements will be taken for:

Insulin, Amino acids, GLP-1, GIP, Ghrelin and peptide YY (PYY).

The measurable end points for this protocol are:

1. Gut hormones levels in response to the 2 methods of AA delivery (I.V and oral)

2. Differences in gut hormones levels between young and older subjects when AA's are delivered orally

Protocol 2:

This will explore the second aim. 16 healthy older subjects will be recruited and subdivided randomly into two groups to receive either post absorptive or postprandial insulin concentrations with or without GLP-1 at physiological ranges in a cross over fashion . During acute study parameters of muscle glucose and amino acids metabolism will be tested together with muscle microvascular recruitment and macro vascular flow in the tested leg.

The measurable end points for this protocol are:

1. Muscle Glucose uptake, assessed by measuring 2-deoxyglucose (2-DOG) phosphate in muscle biopsies

2. Myofibrillar protein synthesis, assessed via muscle biopsy fractional synthesis rate (FSR)

3. Whole Leg Muscle Protein Synthesis, assessed via Arterial-Venous difference (AV method)

4. Whole Leg Muscle Protein Breakdown, assessed via AV method

5. Whole Leg Net Protein Balance, assessed via AV method

6. Muscle microvascular recruitment, assessed via microvascular contrast bubbles filling and refilling post destruction by ultrasound waves. ;

Related Conditions & MeSH terms

• Sarcopenia

• NCT number: NCT02370745
• Study type: Interventional
• Source: University of Nottingham
• Status: Completed
• Phase: N/A
• Start date: November 2014
• Completion date: March 2018