NCT02370745

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

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
• Phase: N/A
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: University of Nottingham · Academic / Other
• Sex: Male
• Age: 18 Years – 75 Years
• Healthy volunteers: Accepted

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)

Detailed 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.

Conditions

• Sarcopenia

Interventions

Type	Name	Description
DRUG	GLP-1	GLP-1 effects on skeletal muscle glucose and amino acid metabolism and microvascular blood flow will be scrutinised under the specified insulin concentrations. It will also be used to test the effect of intravenous feed on insulin secretion.
DRUG	Insulin Actrapid	Skeletal muscle metabolic and microvascular parameters will be tested under specified insulin concentrations with or without GLP-1
DIETARY_SUPPLEMENT	Oral amino acids	Oral amino acids containing 15 g of amino acids
DRUG	GIP	This will be co infused with GLP-1 and intravenous amino acids
DRUG	Intravenous amino acids	This will aim to deliver iso equivalent amount to the amino acids administered orally

Timeline

• Start date: 2014-11-01
• Primary completion: 2018-03-01
• Completion: 2018-03-01
• First posted: 2015-02-25
• Last updated: 2018-05-02

Locations

1 site across 1 country: United Kingdom