Insulin and Sarcopenia in the Elderly
Condition: Sarcopenia
MeSH terms: Sarcopenia
Study type: Interventional
Phase: Phase 1

Summary: 
      Muscle loss with aging is a significant contributor to disability in older people. Our
      general hypothesis is that loss of muscle with aging, known as sarcopenia, may be due to
      inability of muscle to grow in response to insulin. Our goal is to determine the mechanisms
      underlying this age-related insulin resistance of muscle proteins, which will allow us to
      define in the future specific interventions to target this defect and provide the scientific
      basis for the prevention and treatment of sarcopenia.
    

Detailed description: 
      Our general hypothesis is that a reduced response of muscle protein anabolism to insulin
      plays an important role in the loss of muscle mass with aging. Our goal is to determine the
      mechanisms underlying the age-related insulin resistance of muscle proteins, which will allow
      us to define specific interventions to target this defect and provide the scientific basis
      for the prevention and treatment of sarcopenia.

      Our previous studies indicate that the response of muscle proteins to the anabolic action of
      insulin is impaired in healthy older adults as compared to younger controls, which hampers
      the anabolic effect of mixed feeding on muscle proteins. These changes are associated with an
      age-related reduction in the vasodilatory response to insulin, which, from our data, appears
      to be a potentially important mediator of the physiological anabolic effect of insulin on
      muscle proteins. Preliminary data from our laboratory also suggest that in older subjects a
      single bout of aerobic exercise may restore the normal response of blood flow, muscle protein
      synthesis and anabolism to insulin.

      Therefore, we will test in healthy subjects the following specific hypotheses:

        1. Insulin-induced increases in blood flow and muscle perfusion are necessary for the
           physiological stimulation of muscle protein synthesis and anabolism by insulin.

        2. Aging reduces the vascular sensitivity to insulin, which prevents the physiological
           increase in blood flow and muscle perfusion in response to insulin, thereby decreasing
           the response of muscle protein synthesis and net balance to the anabolic action of
           insulin and mixed feeding.

        3. Aerobic exercise can restore, in older subjects, the insulin-induced increase in blood
           flow and muscle perfusion to youthful levels, thus normalizing the anabolic effect of
           insulin and mixed feeding on muscle protein synthesis and net muscle protein balance.

      We will use state-of the art stable isotope tracer techniques to measure muscle protein
      turnover, and a newly developed method to measure muscle perfusion in young and older
      subjects. The results of these studies will allow us to better define the physiological
      mechanisms of action of insulin on muscle protein anabolism, advance our knowledge on the
      pathophysiology of sarcopenia, and provide the scientific basis for the behavioral and/or
      pharmacological treatment of muscle loss with aging.
    

Intervention name(s): Insulin Regular; L-NMMA; Sodium Nitroprusside; mixed meal
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): insulin, 0.2 mU/kg/min for 3 hours; variable rate for 3 hours; variable rate for 3 hours; mixed meal
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Nitroprusside
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: sarcopenia; aging; muscle metabolism