The impact of dietary nitrate ingestion on muscle protein synthesis in elderly type II diabetics

In general, aging is associated with the development of sarcopenia; a gradual,
yet progressive, age-related loss of skeletal muscle mass and strength leading
to impairment in muscle function, disability and a loss of independence. This
reduction in muscle quality, in combination with changes to muscle metabolic
regulation, increase the overall risk of developing chronic metabolic disease
such as type II diabetes. Sarcopenia is assumed to be related to the impaired
muscle protein synthetic response to protein and/or amino acid administration
in the elderly compared with the young. This attenuated response may be a
consequence of the blunted insulin-stimulated increase in
endothelial-dependent-nitric oxide (NO) vasodilation, potentially limiting
amino acid perfusion and subsequent protein synthesis. As such, any
insulin-dependent action is further compromised in elderly individuals living
with type 2 diabetes. Not surprisingly, these individuals commonly experience a
dysregulation of NO metabolism because of the hampered insulin-activated NO
synthase (NOS). Interestingly, numerous reports have linked a diet high in
nitrate (from leafy green vegetables) with a decrease in the prevalence of type
2 diabetes. Nitrate supplementation may possess the ability to improve NO
metabolism independent of insulin through the NO3-NO2-NO pathway. Any
improvement in NO-mediated vasodilation may increase amino acid perfusion
leading to increased postprandial muscle protein synthesis. However, no study
has tested the impact of nitrate ingestion on postprandial muscle protein
synthesis in elderly type 2 diabetics.

To investigate whether the in vivo postprandial muscle protein synthetic
response is augmented when dietary nitrate ingestion precedes protein ingestion
in elderly type 2 diabetics.

Double-blind, parallel-design, placebo controlled study.

1 bolus ingestion of sodium nitrate (NaNO3-) (0.1 mmol NO3- /kg body weight) or
an equalmolar amount of sodium chloride (NaCl) (placebo) dissolved in water and
ingested 2.5 h prior to the ingestion of 20 g of intrinsically labelled casein
protein.

The risks involved in participating in this experiment are minimal. 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 also true for 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. Muscle
biopsies will only be obtained by an experienced physician. The test beverages
contain intrinsically labeled dietary protein which is safe for human
consumption and have been used in previous studies (MEC 06-3-064, MEC 07-3-086,
MEC 09-3-078.3). The labeled, non-radioactive amino acids tracers that will be
infused intravenously are produced according to GMP standards and are safe for
human use. The sodium nitrate has no side effects and specifically produced for
human consumption.