The Effect of the Interaction of Glucagon and Insulin on Endogenous Glucose Production in Humans
Condition: Healthy
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this research is to help understand the relative importance of changes in
      insulin secretion (which lowers glucose) and changes in glucagon (which raises glucose) to
      regulate metabolism and the body's ability to make glucose.
    

Detailed description: 
      Study A (Insulin 0.4mU/Kg/min): Subjects will be admitted to the CRTU at approximately 1700
      on the day prior to study. They will then consume a standard 10kcal/kg meal (55%
      carbohydrate, 30% fat, 15% protein, caffeine free) and fast overnight. Blood will then be
      sampled for baseline enrichment and 2H20 (1.67g/kg of body water) will be given in 3 divided
      doses at 2200, 2400 and 0200. The following morning (approximately 0530), a forearm vein will
      be cannulated to allow infusions to be performed. In addition, a cannula will be inserted
      retrogradely into a vein of the contra-lateral dorsum of the hand. This will be placed in a
      heated Plexiglas box maintained at around 120oF to allow sampling of arterialized venous
      blood. At approximately 0600 (-180 min), a primed, (10microCi prime, 0.1microCi/min
      continuous) infusion containing trace amounts of glucose labeled with [3-3H] glucose will be
      started and continued till 0900 (0 min).

      At 0900 (0 min), the infusion will be varied so as to mimic the anticipated pattern of fall
      of EGP. In addition, glucose also labeled with [3-3H] glucose will be infused so as to
      maintain glucose concentrations at ~ 95mg/dL. Peripheral venous glucose concentrations will
      be measured every 10 minutes to allow the infusion rate of glucose to be adjusted as
      necessary.

      Simultaneously, an infusion of somatostatin (60ng/kg/min) will be started at time 0 to
      inhibit endogenous islet secretion and therefore ensure identical portal insulin
      concentrations on the two study days. Insulin will be infused at a constant rate known to
      produce ~ 50% suppression of EGP (0.4mU/Kg/min).

      From 0900 (0 min) to 1030 (90 min) no glucagon will be infused. Subsequently, a glucagon
      infusion will commence (91 - 180 min) at 0.35 ng/Kg/min and then increase to 0.70 ng/Kg/min
      (181- 270 min), a rate which will be maintained till the end of the study (1330).

      Study B (0.8mU/Kg/min): Approximately 1-2 weeks after the first study visit, subjects will be
      asked to return to the CRTU. This study visit will be similar to Study A. However, insulin
      will be infused at 0.8mU/Kg/min 0 to 270 minutes.
    

Intervention name(s): 0.4mU Insulin followed by withdrawal period followed by 0.8mU study; 0.8mU Insulin followed by withdrawal period followed by 0.4mU study
Intervention type(s): Drug; Drug
Intervention description(s): Clamp study with insulin infused at 0.4 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.8 mU/Kg/min; Clamp study with insulin infused at 0.8 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.4 mU/Kg/min
Other intervention name(s): 0.4 then 0.8; 0.8 then 0.4
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science