Modulating Glucose Tolerance With Dietary Tyrosine
Condition: Glucose Tolerance
Study type: Interventional

Summary: 
      Metabolic or Bariatric surgery is an effective treatment for type 2 diabetes mellitus (T2DM)
      diabetes associated with obesity. There remain some questions about the biochemical mechanism
      that drive how these surgeries work to reverse hyperglycemia. In the proposed human studies,
      the investigators will test the hypothesis that the amino acid tyrosine is a key metabolite
      in regulating blood sugar levels and that manipulation of the amount tyrosine supplied by
      nutrition is able to achieve some of the metabolic benefits seen in the early post-surgical
      period following bariatric surgery. The central hypothesis is that that the tyrosine content
      of the meal challenge affects post-prandial intestinal and plasma dopamine and levodopa and
      L-3,4-dihydroxyphenylalanine (L-DOPA) levels, which, in turn, impact β-cell insulin secretion
      and glucose excursions. The investigators now propose to characterize the possible effects of
      manipulating dopamine and L-DOPA levels in the gut and plasma on glucose tolerance, insulin
      secretion, and insulin sensitivity in healthy volunteers with a range of body mass indexes
      (BMIs).
    

Detailed description: 
      Several biochemical mechanisms explaining how Roux-en-Y Gastric Bypass (RYGB) provides an
      effective treatment for obesity associated type 2 diabetes mellitus (T2DM) and improves
      hyperglycemia independently of weight loss have been proposed. Two are of particular
      interest; a) the hindgut hypothesis suggesting that nutrient delivery to the distal intestine
      drives the production of "incretins" which enhance insulin secretion (e.g. glucagon-like
      peptide-1 (GLP-1)), and b) the foregut hypothesis, positing that foregut bypass reduces the
      secretion of factors (i.e. anti-incretins) that normally defend against hypoglycemia. The
      investigators have been actively investigating this topic and have developed a hypothesis
      based on past studies that they wish to test in a limited human clinical study. In addition,
      preclinical data suggest that there exists a gut-to-beta cell pathway, responsive to
      nutritional tyrosine, regulating insulin secretion, and this pathway provides a mechanism for
      the early postoperative improvements in hyperglycemia observed in RYGB.
    

Intervention name(s): Tyrosine (TYR) Supplementation
Intervention type(s): Dietary Supplement
Intervention description(s): L-Tyrosine dietary supplement will be provided as 500 mg capsules and 4 (four) 500 mg capsules are to be given before OGTT. The capsules are formed from animal gelatin, and the contents are formulated with magnesium stearate as a flow agent, but without binders, coatings or colorings and also have no added flavorings, sugars, salt, artificial sweeteners, preservatives or salicylates. The capsules are to be administered with less than eight ounces of water to minimize dilution of gastric acidity.
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Glucose tolerance; Tyrosine