Dynamics of Muscle Mitochondria in Type 2 Diabetes (DYNAMMO T2D)
Condition: Insulin Resistance
MeSH terms: Insulin Resistance
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells
      for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes
      occurs when the cells of the body become resistant to the effects of insulin, and this causes
      high blood sugar and contributes to a build-up of fat in muscle, pancreas, liver, and the
      heart. Understanding how insulin resistance occurs will pave the way for new therapies aimed
      at preventing and treating type 2 diabetes.

      Mitochondria are cellular structures that are responsible for turning nutrients from food,
      into the energy that our cells run on. As a result, mitochondria are known as "the powerhouse
      of the cell." Mitochondria are dynamic organelles that can move within a cell to the areas
      where they are needed, and can fuse together to form large, string-like, tubular networks or
      divide into small spherical structures. The name of this process is "mitochondrial dynamics"
      and the process keeps the cells healthy. However, when more food is consumed compared to the
      amount of energy burned, mitochondria may become overloaded and dysfunctional resulting in a
      leak of partially metabolized nutrients that can interfere with the ability of insulin to
      communicate within the cell. This may be a way for the cells to prevent further uptake of
      nutrients until the current supply has been exhausted. However, long term overload of the
      mitochondria may cause blood sugar levels to rise and lead to the development of type 2
      diabetes.

      This study will provide information about the relationship between mitochondrial dynamics,
      insulin resistance and type 2 diabetes.
    

Detailed description: 
      The traditional view of mitochondria as isolated, spherical, energy producing organelles is
      undergoing a revolutionary transformation. Emerging data show that mitochondria form a
      dynamic networked reticulum that is regulated by cycles of fission and fusion. The discovery
      of a number of proteins that regulate these activities has led to important advances in
      understanding human disease. Data show that activation of dynamin related protein 1 (Drp1), a
      protein that controls mitochondrial fission, is reduced following exercise in prediabetes,
      and the decrease is linked to increased insulin sensitivity and fat oxidation. The proposed
      research will test the hypothesis that mitochondrial dynamics is a key mechanism of insulin
      resistance in type 2 diabetes. Translational first-in-man studies will use an acute lipid
      challenge to investigate the physiological significance of altered skeletal muscle
      mitochondrial dynamics on insulin sensitivity in humans. The experimental approach harnesses
      innovative molecular and cellular tools, interfaced with physiologically significant human
      studies to obtain meaningful data on insulin resistance, and has the potential to generate
      insights that will lead to new diabetes therapies for future generations.
    

Intervention name(s): Intralipid; Saline
Intervention type(s): Drug; Drug
Intervention description(s): 0.55 ml/kg/h; 0.55 ml/kg/h for
Other intervention name(s): Liposyn
Intervention MeSH terms: Soybean oil, phospholipid emulsion
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Mitochondrial Dynamics; Insulin Resistance