Characterizing the Incretin Effect of Amino Acids and Defining GLP-1 Role on Skeletal Muscle
Condition: Sarcopenia
MeSH terms: Sarcopenia
Study type: Interventional

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.
    

Intervention name(s): GLP-1; Insulin Actrapid; Oral amino acids; GIP; Intravenous amino acids
Intervention type(s): Drug; Drug; Dietary Supplement; Drug; Drug
Intervention description(s): 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.; Skeletal muscle metabolic and microvascular parameters will be tested under specified insulin concentrations with or without GLP-1; Oral amino acids containing 15 g of amino acids; This will be co infused with GLP-1 and intravenous amino acids; This will aim to deliver iso equivalent amount to the amino acids administered orally
Other intervention name(s): Incretin; Actrapid; mixed EAA; Incretin; IV AA
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Incretins
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Incretin; GLP-1; Skeletal muscle metabolism; Microvascular recruitment; Amino Acids; Microvascular blood flow