Post prandial muscle perfusion and protein metabolism in healthy young and elderly men

Age related muscle loss (sarcopenia) is assumed to be related to the impaired
postprandial muscle protein synthetic response to protein and/or amino acid
administration in the elderly vs the young. Increased insulin secretion affects
skeletal muscle blood flow and may therefore affect substrate availability and
postprandial muscle protein synthesis. However, it is unclear whether the
anabolic resistance in the elderly can be explained by a reduced muscle
perfusion due to a diminished response to insulin after protein ingestion.
Hypothesis: Increased local insulin supplementation can reverse the blunted
post-prandial muscle protein synthetic response in the elderly, whereas local
insulin supplementation does not affect the post-prandial muscle protein
synthetic response in the young.

The primary objective of the study is to investigate whether local insulin
supplementation augments the in vivo postprandial muscle protein synthetic
response after protein ingestion and whether this response is differs between
young and elderly subjects. The secondary objective of the study is to assess
the effect of local insulin supplementation on femoral and leg blood flow and
on microvascular perfusion in young and elderly subjects.

Single-blind, placebo controlled, parallel, human intervention study.

The intervention consist of a single test day during which the subjects will
receive a drink containing 20 gram intrinsically labelled casein followed by
local administration of insulin or saline (placebo). In addition, continuous
intravenous tracer infusions will be applied. During the test day 54 plasma
samples and 3 muscle biopsies are collected over a period of 8 h. Furthermore,
femoral blood flow, leg blood and microvascular perfusion will be determined
using Doppler ultrasound, dye dilution and sidestream darkfield imaging (SDF)
in sublingual position, respectively.

Insertion of the catheters in a vein is comparable to a normal blood draw and
the only risk is a small local hematoma. This is the same for the muscle
biopsies. Muscle biopsies will be taken through a small (5 mm) incision,
following local anesthetics of the skin and muscle fascia, and will heal
completely. The insertion of the arterial and venous catheter in the leg may
feel uncomfortable, but once the catheter is in place, the pain lessens. To
minimise the risk of infection, only sterile materials will be used and the
line will be removed directly after completing the test. To prevent bleeding
after withdrawal of the catheters, pressure will be applied to the leg for at
least 10 min followed by a bed rest of another 4 hours to prevent bleeding.
However, there is a risk for a small local hematoma. Finally, a small chance
exists that blood clots can be formed in and around the catheter. This risk
will be minimized by regularly flushing the catheter with sterile saline
containing 1% heparin as an anticoagulant. Such a study with femoral arterial
and venous lines has been previously conducted successfully at the University
of Maastricht (METC 98-030.3). Muscle biopsies and the insertion of the
arterial and venous catheters will only be obtained by experienced physicians.
The test beverages contain intrinsically labeled dietary protein that is safe
for human consumption and has been used in previous studies (METC 06-3-064,
METC 07-3-086, METC 09-3-078.3). The labeled amino acids tracers that will be
infused intravenously are not radioactive and are completely safe, furthermore,
these solutions are produced according to GMP standards.